Forskningsartikler

BACKGROUND: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanisms underlying delirium, particularly in relation to the KP, remain elusive.
METHODS: We undertook a multicenter observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and 1-year mortality.
RESULTS: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA) (OR 2.26 [1.78, 2.87], P < 0.001) to be increased and also found increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL) (β 0.43, P < 0.001) and was a strong predictor of 1-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, P < 0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.
CONCLUSION: Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.

Leiv Otto Watne, Christian Thomas Pollmann, Bjørn Erik Neerland, Else Quist-Paulsen, Nathalie Bodd Halaas, Ane-Victoria Idland, Bjørnar Hassel, Kristi Henjum, Anne-Brita Knapskog, Frede Frihagen, Johan Raeder, Aasmund Godø, Per Magne Ueland, Adrian McCann, Wender Figved, Geir Selbæk, Henrik Zetterberg, Evandro F Fang, Marius Myrstad, Lasse M Giil

Beboere med covid-19-sykdom på norske sykehjem hadde høy risiko for alvorlig forløp og død. Hensikten med denne studien var å utforske sykehjemslegers erfaringer med å ivareta behandlingsansvaret for beboere med covid-19 og hvordan de samarbeidet med pårørende og sykepleiere. Denne intervjustudien inkluderte ti sykehjemsleger med erfaring fra covid-19 i sykehjem fra tre av de fire helseregionene i Norge. Vi gjorde en kvalitativ innholdsanalyse av de transkriberte intervjuene. Analysen identifiserte følgende tre hovedfunn: 1) Krevende ansvar for medisinskfaglige vurderinger og avgjørelser, 2) Kommunikasjon og samarbeid med pårørende – viktig og tidkrevende, og 3) Sykepleierne – en viktig samarbeidspartner. Sykehjemslegene opplevde et krevende ansvar og utfordringer med å ivareta multimorbide og skrøpelige beboere under pandemien. Dette illustrerer behovet for gode rutiner samt lokale og nasjonale retningslinjer. Samarbeidet med erfarne og rutinerte sykepleiere ga trygghet. Sykehjemslegenes beskrivelse av følelsesmessige utfordringer under covid-19-pandemien understreker behovet for faste, kollegiale og faglige nettverk.

Signe Gunn Julnes, Bjørn Lichtwarck, Siren Eriksen, Adelheid Hummelvoll Hillestad, Anita Nilsen, Signe Tretteteig og Anne Marie Mork Rokstad

Objective: To study the association between hearing loss severity, hearing aid use, and subjective memory complaints in a large cross-sectional study in Norway.

Methods: Data were drawn from the fourth wave of the Trøndelag Health Study (HUNT4 Hearing, 2017–2019). Hearing threshold was defined as the pure tone average of 0.5, 1, 2 and 4 kHz in the better ear. The participants were divided into five groups: normal hearing or slight/mild/moderate/severe hearing loss. Subjective self-reported short-term and long-term memory complaints was measured by the nine-item Meta-Memory Questionnaire (MMQ). The sample included 20,092 individuals (11,675 women, mean age 58,3 years) who completed both hearing and MMQ tasks. Multivariate analysis of variance (adjusted for covariates of age, sex, education, and health cofounders) was used to evaluate the association between hearing status and hearing aid use (in the hearing-impaired groups) and long-term and short-term subjective memory complaints.

Results: Multivariate analysis of variance, followed by univariate ANOVA and pairwise comparisons showed that hearing loss was associated only with more long-term subjective memory complaints and not with short-term subjective memory complaints. In the hearing-impaired groups, the univariate main effect of hearing aid use was only observed for subjective long-term memory complaints and not for subjective short-term memory complaints. Similarly, the univariate interaction of hearing aid use and hearing status was significant for subjective long-term memory complaints and not for subjective short-term memory complaints. Pairwise comparisons, however, revealed no significant differences between hearing loss groups with respect to subjective long-term complaints.

Conclusion: This cross-sectional study indicates an association between hearing loss and subjective long-term memory complaints, but not with subjective short-term memory complaints. In addition, an interaction between hearing status and hearing aid use for subjective long-term memory complaints was observed in hearing-impaired groups, which calls for future research to examine the effects of hearing aid use on different memory systems.

Shahram Moradi, Bo Lars Engdahl, Aud Johannessen, Geir Selbæk, Lisa Aarhus og Gro Gade Haanes

Background: Psychosis is a debilitating syndrome occurring in 40-60% of people with Alzheimer’s disease (AD) and corresponds with a more severe disease course. Evidence suggests that psychosis in AD (AD+P) is associated with a distinct profile of neurobiological changes, but little is known about the molecular processes driving etiology. In this study we performed an epigenome-wide association study (EWAS) to investigate DNA methylation associated with AD+P in the dorsolateral prefrontal cortex of 192 post-mortem brain samples.
Method: Brain samples with corresponding in life neuropsychiatric assessments were obtained from the University of Pittsburgh Alzheimer’s disease Research Center (PITT-ADRC). AD pathology was assessed and classified using CERAD neuritic plaque density score, Braak neurofibrillary tangle stages and NIA-RI criteria. The presence or absence of delusions and hallucinations was scored on the CERAD Behavioral Rating Scale. DNA was extracted, bisulfite treated and then profiled on the Illumina Methylation EPIC Array.
Result: After data processing and quality control we used linear regression models to compare 152 AD+P samples to 40 AD samples without psychosis (AD-P). A regional analysis of spatially correlated p-values highlighted four differentially methylated regions (DMRs) associated with psychosis, which are being replicated in other data sets and validated for cell specificity using fluorescence activated nuclei sorting (FANS).
Conclusion: The development of effective therapies for AD+P is an urgent priority. To address this we have collated a well powered study cohort to interrogate the epigenetic basis of AD+P, finding significant methylomic variation. This variation provides an insight into potential mechanisms and biomarkers which will help to identify drug targets and enable better treatment with existing medications.

Luke Stephen Weymouth, Morteza P Kouhsar, Byron Creese, Sverre Bergh, Yehani Wedatilake, Ali Torkamani, Adam R. Smith, Geir Selbaek, Robert Sweet, Clive G Ballard, Jonathan Mill, Julia Kofler, Ehsan Pishva, Katie Lunnon

The overall aim was to explore the prevalence and persistent regular prescription of opioids and paracetamol among nursing home (NH) residents with dementia at admission and over time. A total of 996 residents with dementia, mean (SD) age 84.5 (7.6) years and (36.1% men), were included at admission (A1). Yearly assessments were performed for two years (A2 and A3) or until death. Pain was assessed using the Mobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) Pain Scale. Information regarding prescription of analgesics, general physical health, personal activities of daily living, severity of dementia, neuropsychiatric symptoms, and prescription of psychotropic drugs was collected. A generalized linear mixed model was used to explore whether pain severity was associated with persistent and persistent prescription of opioids and/or paracetamol across timepoints. At A1, 495 of 996 (49.7%) NH residents were prescribed analgesics and prevalence increased at the follow-ups (A2: n = 630, 65.1%; A3: n = 382, 71.2%). Paracetamol was the most frequently prescribed analgesic at all assessments (A1: 45.5%; A2: 59.5%; A3: 67.1%). Opioid prescriptions were quite prevalent (A1: 18.1%; A2: 25.1%; A3: 28.3%), with odds approximately 13 times (OR = 13.3, 95% CI 6.8–26.0) and 9 times (OR = 8.6, 95% CI 3.7–20.3) higher for prescription at follow-up A2 and A3, respectively, relative to prescription at A1. In adjusted analyses, higher pain intensity and poor physical health were associated with prescription and persistent prescription of opioids and paracetamol. In conclusion, prevalence and persistent prescription of analgesics were high in NH residents with dementia. The odds for the prescription of opioids at follow-up were high if prescribed at baseline. Interdisciplinary collaboration, routine assessment of pain at admission and regularly thereafter, and systematic drug reviews are essential to adequately assess and treat pain in NH residents with dementia.

Anne-Sofie Helvik, Sverre Bergh, Kamile Kabukcuoğlu, Jūratė Šaltytė Benth, Bjørn Lichtwarck, Bettina Husebø, Kjerstin Tevik

Vold, overgrep, utelatt helsehjelp, forsømmelser og aggresjon er begreper som beskriver uønskede hendelser i sykehjem. Samtidig er det ingen enhetlig oppfatning av hvordan disse begrepene forstås eller brukes. I denne artikkelen ser vi nærmere på de mest brukte begrepene og hva som kan være en hensiktsmessig begrepsbruk som er gjenkjennbar både i forskning og praksis. Begrepsavklaring er viktig fordi det former synet og holdningene til beboerne, de ansatte og sykehjemmet. Beboere i norske sykehjem har sammensatte behov, og sykehjemmet er en svært kompleks organisasjon. Kompleksitetsteorien og den kontekstuelle teorien om overgrep vektlegger at multifaktorielle og komplekse fenomener må forstås gjennom kontekstuell kunnskap. Hver hendelse av overgrep, utelatt helsehjelp og aggresjon krever en bred tilnærming og utredning utover individuelle egenskaper hos beboeren eller den ansatte. Vi foreslår en begrepsbruk hvor vi skiller mellom begrepene, og beskriver det som faktisk skjer, for å unngå å bruke fellesbetegnelser for mange ulike hendelser. Vi anbefaler også at begreper med stor negativ og normativ valør, som vold og forsømmelser som sekkebetegnelser, bør unngås, spesielt der en antyder en individuell intensjon om å skade.

Astrid Sandmoe, Janne Myhre, Maria Hélen Iversen, Siren Eriksen and Bjørn Lichtwarck

Sammendrag

Seksuelle relasjoner mellom personer med demens som bor på sykehjem, kan skape utfordringer. Demenssykdommer kjennetegnes av kognitiv svikt og kan påvirke personers evne til å ta beslutninger og forstå konsekvenser. Mye tyder på at helselovgivningen ikke gir helse- og omsorgspersonell god nok veiledning når utfordringer oppstår.

I artikkelen drøftes ulike helserettslige utfordringer med utgangspunkt i et empirisk eksempel. Utfordringene omhandler de sykehjemansattes vurdering av plikt og anledning til å gripe inn i en seksuell relasjon, vurdering av frivillighet, vurdering av samtykkekompetanse og involvering av pårørende. Disse komplekse problemstillingene der ulike verdier, faglig kompetanse, menneskerettigheter, helselovgivning og straffebestemmelser må veies opp mot hverandre og ses i sammenheng, ofte av ansatte uten juridisk kompetanse, krever tiltak for å sikre en mer enhetlig tilnærming og likebehandling av personer med demenssykdom på sykehjem. Det økende antallet personer med demens i Norge krever at disse utfordringene får større juridisk oppmerksomhet, og dagens regelsett må ses i sammenheng og lovforståelsen tydeliggjøres i for eksempel faglige veiledere.

Kjersti Wilson, Anne-Lene Egeland Arnesen, Kariann Krohne and Siren Eriksen

Background: Healthcare workers (HCWs) are central and serve in the frontlines when epidemics threaten public health. Thus, certain communities may be hardest hit by these challenges. Interventions supporting HCWs are important, and to develop these, understanding their experiences is essential.

Aim: To explore how HCWs in Norwegian public in-home services experienced work during the COVID-19 pandemic over time.

Method: A longitudinal qualitative study with two data collections approximately one year apart (2021 and 2022) was performed. Individual interviews were conducted with HCWs.

Results: The analysis resulted in six main themes: Changing everything, Redefining ‘necessary tasks’, Distancing and loneliness, Cooperation and coordination, More infections and fewer worries and Lessons for the future. These indicate capabilities and processes, how they are evolving over time, and outcomes. The first two themes focus on the first period of the pandemic, the next two on the ongoing intermediate period, and the final two cover the last period.
Conclusion: The HCWs’ narratives have demonstrated their collective coping based on adaptive and transformative capacities. Further, they have enlisted experienced social resilience in their strategies for coping with the COVID-19 challenges.

Aud Johannessen, Anne-Sofie Helvik, Kjerstin Elisabeth Tevik and Kirsten Thorsen

Objectives: This meta-aggregation aims to interpret and synthesize present knowledge on the lifeworld perspectives of people with dementia and develop a model for guidance in clinical practice.

Method: The data consist of four meta-syntheses describing different lifeworld perspectives in accordance with van Manen’s existentials: lived relations, lived space, lived time and lived body. The meta-aggregation summarizes a range of views expressed by people with dementia in qualitative, interview-based studies, with the aim of generating a reliable model based on the studies’ findings.

Results: In total, 88 studies among 1,191 persons with dementia were included. Sixteen areas of focus were found, representing four perspectives: (a) lived relations, consisting of connectedness, independence, equality and competence; (b) lived space, consisting of belonging, meaningfulness, safety and security, and autonomy; (c) lived time, consisting of being rooted in the past, being in the present, viewing the future and being in process; and (d) lived body, consisting of being functional, trustworthy, adaptable and presentable. A model shaped as a tree trunk captures the lifeworld perspectives of people with dementia.

Conclusion: Sixteen areas were revealed from this meta-aggregation and form the basis of a model. This model may be used as a guide for health care personnel to ensure the overall lifeworld-perspectives of people with dementia in care for the target group and conduct lifeworld-preserving care with a person-centred approach.

Siren Eriksen, Knut Engedal and Ellen Karine Grov