Forskningsartikler

Background: Mobility impairments, in terms of gait and balance, are common in persons with dementia. To explore this relationship further, we examined the associations between mobility and cerebrospinal fluid (CSF) core biomarkers for Alzheimer’s disease (AD).
Methods: In this cross-sectional study, we included 64 participants [two with subjective cognitive decline (SCD), 13 with mild cognitive impairment (MCI) and 49 with dementia] from a memory clinic. Mobility was examined using gait speed, Mini-Balance Evaluation Systems test (Mini-BESTest), Timed Up and Go (TUG), and TUG dual-task cost (TUG DTC). The CSF biomarkers included were amyloid-β 42 (Aβ42), total-tau (t-tau), and phospho tau (p-tau181). Associations between mobility and biomarkers were analyzed through correlations and multiple linear regression analyses adjusted for (1) age, sex, and comorbidity, and (2) SCD/MCI vs. dementia.
Results: Aβ42 was significantly correlated with each of the mobility outcomes. In the adjusted multiple regression analyses, Aβ42 was significantly associated with Mini- BESTest and TUG in the fully adjusted model and with TUG DTC in step 1 of the adjusted model (adjusting for age, sex, and comorbidity). T-tau was only associated with TUG DTC in step 1 of the adjusted model. P-tau181 was not associated with any of the mobility outcomes in any of the analyses.
Conclusion: Better performance on mobility outcomes were associated with higher levels of CSF Aβ42. The association was strongest between Aβ42 and Mini-BESTest, suggesting that dynamic balance might be closely related with AD-specific pathology.

Gro Gujord Tangen, Karen Sverdrup, Kristin Taraldsen, Karin Persson, Knut Engedal, Peter Bekkhus-Wetterberg and Anne-Brita Knapskog

ABSTRACT
Introduction: Half of patients with limited stage small cell lung cancer (LS SCLC) are >70 years, but account for <20% of participants in most trials. Comorbidities, reduced organ- and physical function might lead to more treatment toxicity and population-based studies indicate that fewer older than younger LS SCLC patients receive standard chemoradiotherapy, although there is limited evidence for such a policy.
Methods: We compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health related quality of life (HRQoL) and treatment outcomes between patients >70 and <70 years in an open label randomized phase II trial comparing twice-daily thoracic radiotherapy (TRT) of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent platinum/etoposide chemotherapy.
Results: 170 patients who were >18 years and had performance status (PS) 0-2 were randomized. Of these, 53 patients (60 Gy:25, 45 Gy:28) were >70 years and 117 (60 Gy:64, 45 Gy:53) were younger. There were no significant differences in baseline characteristics, treatment completion rates, toxicity, or response rates across age groups. HRQoL mean scores was similar during year one, but older patients reported more decline on functional scales than younger patients during year two. OS was significantly shorter for older patients while there was no significant difference in PFS or TTP.
Conclusion: Patients >70 years tolerated concurrent twice daily chemoradiotherapy and achieved similar disease control as younger patients, indicating that older patients should receive the same treatment as younger patients.

Kristin Toftaker Killingberg, Bjørn Henning Grønberg, Marit Slaaen, Øyvind Kirkevold, Tarje Onsøien Halvorsen

Summary

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer’s disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74–1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71–1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = −0.06 to 0.80). The insomnia symptom “difficulties maintaining sleep” was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67–0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57–0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15–0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes.

Selma Selbæk-Tungevåg, Geir Selbæk, Bjørn Heine Strand, Christian Myrstad, Gill Livingston, Stian Lydersen, Sverre Bergh, Linda Ernstsen

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