Forskningsartikler

Background:
Polygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer’s disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed.
Objective:
The aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations.
Methods:
We used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort (n = 2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort (n = 7,643) and The Copenhagen General Population Study (CGPS) cohort (n = 10,886).
Results:
We showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model.
Conclusion:
PHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.

Ehsan Motazedi, Weiqiu Cheng, Jesper Q Thomassen, Oleksandr Frei, Arvid Rongve, Lavinia Athanasiu, Shahram Bahrami, Alexey Shadrin, Ingun Ulstein, Eystein Stordal, Anne Brækhus, Ingvild Saltvedt, Sigrid B Sando, Kevin S O’Connell, Guy Hindley, Dennis van der Meer, Sverre Bergh, Børge G Nordestgaard, Anne Tybjærg-Hansen, Geir Bråthen, Lasse Pihlstrøm, Srdjan Djurovic, Ruth Frikke-Schmidt, Tormod Fladby, Dag Aarsland, Geir Selbæk, Tyler M Seibert, Anders M Dale, Chun C Fan and Ole A Andreassen

Background:
Differences in survival between groups may reflect avoidable and modifiable inequalities. This study examines the 35-year mortality risk for adults aged 25–44 years in the mid-1980s with disability due to vision, hearing, or motor impairment; physical illness; or mental health problems.
Methods:
This Norwegian study was based on data from the Trøndelag Health Study (HUNT1, 1984–86, and HUNT2, 1995–97) linked to tax-registry data for deaths before 15 November 2019. Mortality risk was estimated by Cox regression analysis adjusted for age and sex. Sensitivity analysis included the following possible mediators: education, work, living situation, body mass index, systolic blood pressure and smoking.
Findings:
Of the 30,080 HUNT1 participants aged 25–44 years, 5071 (16.9%) reported having disability. During the 35 years of follow-up, 1069 (21.1%) participants with disability and 3107 (12.4%) without disability died. Individuals with any type of disability had 62% higher mortality risk compared to those without a disability, adjusted by age and sex. The highest mortality risks were observed for disability due to severe motor impairment (HR=3.67, 95%CI=2.89–4.67) and severe mental health problems (HR=3.40, 95%CI=2.75–4.23) compared to those without these disabilities. Increased mortality risk was found for all the included disability types. The associations were somewhat mediated, especially by education, work and living situation.
Interpretation:
This study shows that among adults aged 25–44 years, the risk of death increases with disability of different types and severity levels, particularly for disability related to mental health problems or motor impairment.

Ellen Melbye Langballe, Gro Gujord Tangen, Bo Engdahl og Bjørn Heine Strand

This study explores the perceptions of Norwegian nurses who have received assisted dying requests from terminally ill patients. Assisted dying is illegal in Norway, while in some countries, it is an option. Nurses caring for terminally ill patients may experience ethical challenges by receiving requests for euthanasia and assisted suicide. We applied a qualitative research design with a phenomenological hermeneutic approach using open individual interviews. A total of 15 registered nurses employed in pulmonary and oncology wards of three university hospitals and home care in one municipality were recruited. Four themes emerged from the analysis: (1) unprepared for the request; (2) meeting direct, indirect, and nonverbal requests; (3) working in a gray zone, and (4) feeling alone and powerless. The study found that nurses were unsure how to handle such requests due to professional uncertainty about assisted dying. Working in an environment where the topic is taboo made nurses morally uncertain, and some perceived this as moral distress. The hospital chaplain played a significant role in providing support to these nurses.

Hege Hol, Solfrid Vatne, Kjell Erik Strømskag, Aud Orøy og Anne Marie Mork Rokstad

Abstract

Background: Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer’s disease (AD).
Objective: In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-β, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls.
Methods: We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-β, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups.
Results: Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p = 0.01) and phosphorylated tau protein (p = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-β in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF.
Conclusion: Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein.

Jelena Zugic Soares, Jørgen Valeur, Jūratė Šaltytė Benth, Anne-Brita Knapskog, Geir Selbæk, Nenad Bogdanovic, Renate Pettersen

Age-related changes and losses may lead to loneliness. However, some people do not become lonelier, even after negative life events. This study examines the development of loneliness based on Norwegian panel data (N = 2,315), age 40–80 years at baseline, and the impacts of partnership and health measured in 2002, 2007, and 2017. We ask: How does loneliness develop over time, and who resists becoming lonely? In the total group, loneliness decreased from 2002 to 2007 and then leveled off. In the eldest age group, 70–80 years at baseline, loneliness increased but only in the last period, from 2007 to 2017. In all age groups and at all three times, those who were not lonely more often had a partner and were more often in good health compared to those who were lonely. Period effects, cohort, and age-related changes influencing the development in loneliness over time are discussed.

Magnhild Nicolaisen, Are Hugo Pripp, Kirsten Thorsen

Cognitive function can be affected by cancer and/or its treatment, and older patients are at a particular risk. In a prospective observational study including patients ≥65 years referred for radiotherapy (RT), we aimed to investigate the association between patient- and cancer-related factors and cognitive function, as evaluated by the Montreal Cognitive Assessment (MoCA), and sought to identify groups with distinct MoCA trajectories. The MoCA was performed at baseline (T0), RT completion (T1), and 8 (T2) and 16 (T3) weeks later, with scores ranging between 0 and 30 and higher scores indicating better function. Linear regression and growth mixture models were estimated to assess associations and to identify groups with distinct MoCA trajectories, respectively. Among 298 patients with a mean age of 73.6 years (SD 6.3), the baseline mean MoCA score was 24.0 (SD 3.7). Compared to Norwegian norm data, 37.9% had cognitive impairment. Compromised cognition was independently associated with older age, lower education, and physical impairments. Four groups with distinct trajectories were identified: the very poor (6.4%), poor (8.1%), fair (37.9%), and good (47.7%) groups. The MoCA trajectories were mainly stable. We conclude that cognitive impairment was frequent but, for most patients, was not affected by RT. For older patients with cancer, and in particular for those with physical impairments, we recommend an assessment of cognitive function.

Guro Falk Eriksen, Jūratė Šaltytė Benth, Bjørn Henning Grønberg, Siri Rostoft, Øyvind Kirkevold, Sverre Bergh, Anne Hjelstuen, Darryl Rolfson and Marit Slaaen