Biomarker and pathology studies in neurodegenerative cognitive impairment

Background: Dementia is a major cause of functional impairment and early death in older age groups. Neurodegenerative disorders are the most common cause of dementia. The most frequent neuropathological lesions include neurofibrillary tangles and senile plaques, hallmark lesions for Alzheimer´s disease (AD), and Lewy body pathology, which characterize Lewy body disease (LBD). Clinically, the neuropathological entity LBD can present as either Parkinson´s disease (PD) or dementia with Lewy bodies (DLB), differentiated on the basis of the presenting symptoms being either motor or cognitive. While the majority of LBD patients develop both motor symptoms and cognitive impairment, some patients with clinical PD will never experience cognitive impairment and likewise some patients with DLB will never develop motor symptoms. Similarly the clinical presentation of AD is also heterogeneous, for instance, the highly variable occurrence of neuropsychiatric symptoms and rate of progression. These differences have a major impact on quality of life for patients and carers, as well as health care costs, but their mechanisms and neuropathological underpinnings are poorly understood. Furthermore the correlation between clinical diagnosis and neuropathological findings is relatively low, and LBD patients presenting with cognitive impairment particularly risk being misclassified as AD. This highlight the need for more precise biomarkers for these clinical syndromes that can be implemented at the start of and during the course of the disease. Biomarkers may inform about disease pathology, thus paving the way for new treatment, they increase diagnostic accuracy and aid in setting a prognosis. Biomarkers are needed in the selection of patients for treatment studies and to identify which patients should benefit from new treatment when available. The cerebrospinal fluid (CSF) biomarkers beta-amyloid 42 (abeta42), total tau (t-tau) and tau protein phosphorylated at amino acid 181 (p-tau181) reflect key AD pathologies. The Lewy bodies found in LBD are composed mainly of the protein !-synuclein. !-synuclein is reduced in CSF in LBD, but with considerable overlap between LBD, controls and other disease groups. Aim: The main aim of this thesis was to increase understanding of pathological mechanisms underlying important clinical features in neurodegenerative cognitive impairment, by exploring the associations between clinical presentation and biomarkers and pathology. The first objective was to explore the association between AD pathology CSF markers and neuropsychiatric symptoms in newly diagnosed AD patients; secondly to assess the association between CSF markers of AD and LBD pathology and early cognitive impairment in PD; thirdly to examine the correlation between clinical diagnosis of DLB and Lewy body pathology at autopsy. Methods: This is a clinical translational neuroscience project based on two clinical cohort studies. The dementia Study of Western Norway (Demvest) included newly diagnosed dementia patients from specialist clinics in geriatric medicine and old age psychiatry in Western Norway. The Parkinson´s Progression Markers Initiative (PPMI) is an international multicentre study, including newly diagnosed PD patients and healthy controls. A comprehensive battery of neuropsychological tests, a structured neuropsychiatric evaluation, clinical examination, and imaging were part of both studies. CSF sampling was done according to standardized protocols and CSF was analysed using commercially available immunoassays. In the Demvest study, participants were recruited for brain donation, and autopsy results were obtained applying commonly used neuropathological protocols and diagnostic criteria. Results: We undertook three specific studies to investigate objective I, II and III. In study I, apathy in patients with early Alzheimer´s disease correlated with t-tau and ptau181 concentrations in CSF, higher values being associated with more severe apathy. There were no associations between depression or psychosis and agitation and CSF markers. In study II, decreased CSF !-synuclein in newly diagnosed PD-patients without dementia correlated with impaired global cognition and impairment of executive functions and attention. CSF abeta42 was decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates. No correlations were found between memory or visuospatial functions and CSF markers. Study III examined autopsy results of 56 patients followed from dementia diagnosis to death. 20 patients received a pathological diagnosis of LBD; the corresponding clinical diagnosis were probable DLB (n=11), Parkinson´s disease with dementia (PDD) (n=5) and probable or possible AD (n=4). Of the 56, 14 patients received a clinical diagnosis of probable DLB, 11 of these had pathological LBD and three AD. Sensitivity, specificity, positive and negative predictive values of a clinical DLB diagnosis were 73%, 93%, 70%, and 90% respectively. Conclusions and implications: We have reported a novel association between neuropsychiatric symptoms and CSF biomarkers reflecting core AD pathology. The relationship between t-tau and p-tau181 and apathy may reflect an association between neurofibrillary tangle pathology and apathy in early AD. Cognitive impairment in early PD was associated with biomarkers of both Lewy body and AD pathology. 18 of 20 LBD patients in the Demvest study had Braak neurofibrillary tangle stage IV or higher, representing severe AD pathology at autopsy. Thus our findings suggest a role for AD pathology in both early and established LBD. Accurate diagnosis is crucial for clinical practice and research. With a sensitivity of 73%, the clinical 2005 DLB criteria are not sensitive enough. More than one in four DLB patients were not identified even when structured rating scales for core DLB symptoms were applied. We regard a specificity of 93% as satisfactory. Our results illustrate that not all DLB patients fulfil the 2005 DLB criteria at disease presentation, highlighting the need for re-evaluation of the diagnosis if new symptoms appear. Studies applying the most recent 2017 DLB criteria will show if this revision has increased sensitivity without decreasing specificity

The Music Producers´ Role in A Digital Era : “An understanding of a how digitalization and the development of the producers’ role over time, has affected the labor practices of the producer and the dynamics between different parts in the industry.”

Master's thesis Music Management MU501 - University of Agder 2018As we all know the Music has been through quite a shift due to the digitalization both in business models and the way it is structured. There has been little research on the way these changes have affected the specific professions within the industry. This paper aims to look at how these changes have affected the Music Producers labor practices, and how the dynamics between the different parts in the industry has changed. It also aims to look at why it has happened, and what it has led to. The paper concludes with the fact that there is a lot of structural changes that has forced the producers to work different in order to stay relevant. Based on semi-structured interviews with informants that work as producers professionally, the paper finishes with a discussion part where the most interesting findings are being linked up to relevant theory within the field

Mixing of the Storfjorden overflow (Svalbard Archipelago) inferred from denstity overturns

Observations were made of the dense overflow from Storfjorden from a survey conducted at closely spaced stations in August 2002. The field data set consists of conventional conductivity-temperature-depth profiles and short-term moored current meters and thermistor strings. Finestructure estimates were made by calculating Thorpe scales over identified overturns using 0.1-dbar vertically averaged density profiles. Dissipation rate of turbulent kinetic energy per unit mass, e, is estimated assuming proportionality between Thorpe and Ozmidov length scales. Vertical eddy diffusivity Kz is estimated using Osborn’s model assuming a constant mixing efficiency. Survey-averaged profiles suggest enhanced mixing near the bottom with values of Kz and e, when averaged within the overflow, equal to 10 x 10-4 m2 s-1 and 3 x 10-8 W kg-1, respectively. Kz is found to decrease with increasing buoyancy frequency as N-1.2 (±0.3), albeit values of N covered only 0.5–8 cph (1 cph = 2p/3600 s-1). Values of heat flux obtained using Kz suggest that the plume gains a considerable amount of heat, 45 ± 25 W m2, when averaged over the thickness of the plume, from overlying waters of Atlantic origin. This value is lower than but, considering the errors in estimates of Kz, comparable with 100 W m2, the rate of change of heat in the overflow derived from sections across the sill and 80 km downstream.publishedVersio

Wind-Driven Variability in the Spitsbergen Polar Current and the Svalbard Branch Across the Yermak Plateau

The Yermak Plateau (YP) acts as a guidance or barrier for the West Spitsbergen Current (WSC), which either crosses the plateau or flows around it to enter the Arctic Ocean. Closer to the West Spitsbergen coast, the Spitsbergen Polar Current (SPC) also flows over the YP in a narrow passage between the Svalbard Branch (SB) and the coast. A 2-year ocean observing program combined with altimetry and re-analysis wind data has given new knowledge on the variability and dynamics of the SPC and SB. The variability in the SPC and SB is controlled by the sea surface pressure gradient driven by the wind stress along the West Spitsbergen coast and locally on the YP. A peak-to-peak volume transport variability of 0.8 Sv and a positive heat transport anomaly of 3 TW were found in the SPC. The variability in the SB is mainly controlled by the upstream wind stress curl field along the West Spitsbergen Shelf where the negative wind stress curl field force the barotropic WSC branch directly into the SB. The peak-to-peak variability in the SB can exceed 4 Sv and in January 2016, an episodic heat flux was estimated to be 10 TW. Hence, an increasing number of winter cyclones affecting Svalbard will increase the volume transport variability and pulses of warm water to the shelf areas north of Svalbard.publishedVersio

A qualitative study of educators' experiences and pedagogical role in kindergarten during the Covid-19 pandemic

Masteroppgave i tilpassa opplæring - Nord universitet 202

Hvordan påvirkes robust tillit mellom leder og medarbeider når arbeidet utføres fra hjemmekontor på ubestemt tid?

Mange populærartikler skriver at tillitt er ferskvare. Hvordan vil det gå med tillit når leder og medarbeider kun har digital kontakt under covid-19? Tillitbasert ledelse forutsetter at det er tett relasjon mellom leder og medarbeider. Hvordan opprettholde denne relasjonen digitalt? Det var utgangspunktet for min studie: Hvordan påvirkes robust tillit i en ekstrem situasjon med avstandsledelse, usikkerhet og kun bruk av digital kommunikasjon? Pandemisituasjonen har gjort at det var en unik mulighet til å forske på dette. Vi har aldri tidligere opplevd lignende ekstreme betingelser med avstandsledelse, som stiller helt nye krav til ledere og medarbeidere. Jeg ville se funnene mine om tillit i sammenheng med tillitbasert styring og ledelse i Oslo kommune. Er det noe å lære av erfaringer med det å lede hele medarbeidergruppen på avstand over så lang tid? For å undersøke dette har jeg spesielt vært opptatt av om ledere brukte kommunikasjon på en måte som førte til at medarbeidernes opplevelse av sosial nærhet ikke ble endret i vesentlig grad. Jeg sammenlignet leder- og medarbeiderperspektivet, for å se om intensjon med tillitbasert styring og ledelse viste seg i praksis. Gjenspeilet medarbeidernes oppfattelse av leders måte å lede, det lederne uttrykte at de ville oppnå med lederskapet sitt? Hovedfunnet var at tillit har blitt opprettholdt gjennom avstandsledelse, men at det er ulikheter når det gjelder graderingen av tillit som er interessant. Det som er nytt med min forskning er at det underveis har vært så godt som ingen form for kommunikasjon ansikt til ansikt mellom leder og medarbeider. Funnene mine er i tråd med tidligere forskning som bekrefter at kommunikasjonen endrer seg når den flyttes til digitale kanaler. Det vi kan lære om avstandsledelse av oppgaven min er at det krever mer av ledere av bevisst individuell oppfølging av medarbeiderne på hjemmekontor for at de skal føle seg ivaretatt. Ledere som har evnet å se at dette var en unik situasjon som krevde nye måter å kommunisere på og som har lyttet til medarbeidernes behov, er de som har opprettholdt tillitsforholdet best. Tilbakemeldinger, kunnskapsdeling og oppfølgingssamtaler er mer krevende digitalt. Det som gir god effekt er korte, hyppige individuelle samtaler med fokus på relasjoner. Tillit fortsetter å være viktig i forholdet mellom leder og medarbeider i tiden framover og anbefalt ledelsesform kan etter mine funn omdøpes til tillitbasert situasjonsbestemt avstandsledelse

Hvordan benytter ungdomspartiene seg av sosiale medier i sin politiske kommunikasjon?

Temaet for denne oppgaven er ungdomspartiers politiske kommunikasjon i sosiale medier. Tall fra datatilsynet i 2013 forteller at 76% av den norske befolkningen har en Facebookprofil. Dette gjør Facebook til et av de viktigste mediene i Norge. Fordelene for politikere ved å være tilstede i sosiale medier kan potensielt være store. Ifølge Marshall McLuhan er det et en utfordring for mennesker å forstå hvordan man kommuniserer i nye medier. Det har nå gått fire år siden 76% av oss hadde Facebookprofil, i dag kan tallet være enda høyere. Vi ville finne ut i hvilken grad ungdomspolitiske partier har lært seg å benytte sosiale medier i sin kommunikasjon. Unge folk har i dag vokst opp med internett og sosiale medier, vi antok at dette kunne være en fordel for ungdomspolitikere. Kanskje hadde ungdomspolitikerne knekt noen koder som moderpartiene deres enda ikke har. Som bakgrunn for bruk og forståelse av sosiale medier har vi brukt Bente Kalsnes sin doktoravhandling «The power of likes: Social media logic and political communication» (2016). Hun redegjør for de ulike handlingsmulighetene sosiale medier har og hvordan politikere, mediene og folket benytter seg av disse. Handlingsmulighetene gir politiske aktører muligheten til å oppsøke og direkte kommunisere med ulike velgergrupper. Benytter en seg av disse mulighetene kan politiske partier potensielt mobilisere avgjørende velgermasser. Det har vist seg å være vanskelig å tilpasse seg de nye mediene. Mye fordi logikken i eldre medier er sterkt iboende i oss. Fra andre verdenskrig har vi hatt ulike faser i mediebruken i Norge. Disse fasene viser at tilpasningen til nye medier er en langsiktig prosess. Kanskje har tilpasningen vært lettere for ungdomspolitikere, fordi de har vokst opp med både tradisjonell og moderne mediebruk om hverandre. Med en kvalitativ metode og dybdeintervjuer har vi forsøkt å få en dypere forståelse for hvordan de ansvarlige for sosiale medier i ungdomspartiene arbeider. Funnene blir knyttet opp til Bente Kalsnes teorier om bruk av sosiale medier, de ulike mediefasene i Norge og Marshall McLuhans teorier om medier. Et annet aspekt vi knytter funnene opp mot er hvilke konsekvenser sosiale medier har for ungdomspartienes makt og oppslutning. Det er to hovedperspektiver på området. Mobiliseringsperspektivet mener sosiale medier gir makt til mindre aktører. Forsterkningsperspektivet mener sosiale medier forsterker etablerte maktstrukturer

Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study

OBJECTIVES: We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. METHODS: Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005–2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. RESULTS: At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). CONCLUSIONS: Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling