Forskningsartikler

ABSTRACT
Purpose The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data.
Participants The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009–2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders.
Findings to date All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources.
Future plans The finish date of NorCog was originally in 2029. In 2021, the registry’s legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.

Ingrid Tøndel Medbøen, Karin Persson, Marit Nåvik, Torunn Holm Totland, Sverre Bergh, Cathrine Selnes Treviño, Ingun Ulstein, Knut Engedal, Anne-Brita Knapskog,  Anne Brækhus, Anne Rita Øksengård, Peter Otto Horndalsveen, Ingvild Saltvedt, Anne Liv Lyngroth, Anette Hylen Ranhoff, Dagny Bekkeheien Skrettingland, Mala Naik, Jelena Zugic Soares, Bente Johnsen, Geir Selbæk

Abstract
Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer’s disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

Iris E. Jansen, Sven J. van der Lee, Duber Gomez-Fonseca, Itziar de Rojas, Maria Carolina Dalmasso, Benjamin Grenier-Boley, Anna Zettergren, Aniket Mishra, Muhammad Ali, Victor Andrade, Céline Bellenguez, Luca Kleineidam, Fahri Küçükali, Yun Ju Sung, Niccolo Tesí, Ellen M. Vromen, Douglas P. Wightman, Daniel Alcolea, Montserrat Alegret,…Sverre Bergh…Geir Selbæk… Wiesje van der Flier

ABSTRACT
Social isolation and feelings of loneliness are main reasons that befriending services are approached by older adults. The promise of an individually matched volunteer, a befriender, paying them regular visits, offers hope of increased social interaction, meaningfulness, and connectedness in everyday life. The current consensus in qualitative research literature is that loneliness and isolation may be alleviated by such home visits. Still, the actual mechanisms of successful befriending have not been identified. In this small-scale qualitative study, we highlight older befriendees’ notions of friendship in befriending. Drawing on in-depth interviews with seven Norwegian befriendees over the age of 80 years, we suggest that having a befriender visit regularly spurs a new bond and supports befriendees’ notions of a relationship consistent with a traditional understanding of friendship. Our findings illustrate how the older befriendees identify and portray notions of friendship in terms of bonding, compatibility and meaningful activities, commitment, appreciation, and insecurities. Understanding how a formalized volunteer service is recognized and valued as a friendship may contribute to a better starting point for improving befriending services. Furthermore, it can improve our understanding of the significance of friendship in old age.

Kariann Krohne, Annelise D. Flor & Magnhild Nicolaisen

Background
The number of older adults with cancer is increasing. Radiotherapy is an important treatment modality in cancer, and may cause side effects and distress. Patient-reported experience measures aim to measure patients’ experience with health care. This can help health care services to improve in line with patients’ needs. To assess how Norwegian patients receiving radiotherapy experience their care, a valid and reliable tool is required. We selected the Person-centred coordinated care experience questionnaire as a tool. The aim of the study is to validate the Norwegian version of this questionnaire in a radiotherapy setting.
Methods
A feasibility study of the Person-centred coordinated care experience questionnaire and a cross-sectional study – testing psychometric properties of the questionnaire in a Norwegian radiotherapy setting – were conducted. Participants were recruited from two different hospitals in Norway. Patient characteristics and item scores are described using descriptive statistics. We performed an exploratory factor analysis, and applied principal component analysis with a varimax rotation. Cronbach’s α was used to assess internal consistency.
Results
24 patients participated in the feasibility test, and 176 were included in the cross-sectional study where we explored the psychometric properties of the Person-centred coordinated care experience questionnaire. Three factors were identified. Internal consistency was established for the ten-item scale, with Cronbach’s α = 0.698.
Conclusion
Conclusions must consider the Norwegian setting and health care context. We found that the Norwegian version of the Person-centred coordinated care experience questionnaire is a relevant, valid, and reliable tool to provide insight into different areas of patients’ experiences upon receiving radiotherapy. However, further testing on a larger sample is necessitated.

May Ingvild Volungholen Sollid, Marit Slaaen, Signe Danielsen, Øyvind Kirkevold

Objectives:
To investigate the presence of awareness of changes in relationships domain, and additional subdomains (cognitive, emotional and functional status) in a group of participants with dementia.
Method:
Using a qualitative design, 9 participants with mild and moderate dementia attended in a day care center were interviewed. Analyses were implemented throughout the modified version of the Grounded Theory Method.
Results:
Some participants well-recognized changes in their relationships, albeit a tendency to immediately deny those changes was observed among them. The participants’ reports showed that the kind of familiar or social relationship might facilitate the expression of awareness. Less discomfort in social interactions with familiars and friends compared to embarrassment with unfamiliar relationships were described. All participants could partially recognize their cognitive deficits, although attempts to normalize their condition and minimize difficulties were identified. Only two participants partially recognized changes in all investigated domains. The other participants partially described changes in two domains beyond the cognitive domain, such as relationships and emotional status or emotional and functional status. However, answers concerning emotional status reflected that some coping styles were not related to a general condition.
Conclusion:
The relationship domain may provide a valuable perspective of awareness of disease. People with dementia may feel less embarrassed to recognize deficits in the presence of familiars and friends.

Paula Gasparini Emery Trindade, Aud Johannessen, Maria Alice Tourinho Baptista, Virgínia Maffiolletti & Marcia Cristina Nascimento Dourado

Background:
The Personal Activity Intelligence (PAI) translates heart rate during daily activity into a weekly score. Obtaining a weekly PAI score ≥100 is associated with reduced risk of premature morbidity and mortality from cardiovascular diseases. Here, we determined whether changes in PAI score are associated with changes in risk of incident dementia and dementia-related mortality.
Methods: We conducted a prospective cohort study of 29,826 healthy individuals. Using data from the Trøndelag Health-Study (HUNT), PAI was estimated 10 years apart (HUNT1 1984–86 and HUNT2 1995–97). Adjusted hazard-ratios (aHR) and 95%-confidence intervals (CI) for incidence of and death from dementia were related to changes in PAI using Cox regression analyses.
Findings:
During a median follow-up time of 24.5 years (interquartile range [IQR]: 24.1-25.0) for dementia incidence and 23.6 years (IQR: 20.8–24.2) for dementia-related mortality, there were 1998 incident cases and 1033 dementia-related deaths. Individuals who increased their PAI score over time or maintained a high PAI score at both assessments had reduced risk of dementia incidence and dementia-related mortality. Compared with persistently inactive individuals (0 weekly PAI) at both time points, the aHRs for those with a PAI score ≥100 at both occasions were 0.75 (95% CI: 0.58–0.97) for incident dementia, and 0.62 (95% CI: 0.43–0.91) for dementia-related mortality. Using PAI score <100 at both assessments as the reference cohort, those who increased from <100 at HUNT1 to ≥100 at HUNT2 had aHR of 0.83 (95% CI: 0.72–0.96) for incident dementia, and gained 2.8 (95% CI: 1.3–4.2, P<0.0001) dementia-free years. For dementia-related mortality, the corresponding aHR was 0.74 (95% CI: 0.59–0.92) and years of life gained were 2.4 (95% CI: 1.0–3.8, P=0.001).
Interpretation:
Maintaining a high weekly PAI score and increases in PAI scores over time were associated with a reduced risk of incident dementia and dementia-related mortality. Our findings extend the scientific evidence regarding the protective role of PA for dementia prevention, and suggest that PAI may be a valuable tool in guiding research-based PA recommendations.

Atefe R. Tari, Geir Selbæk, Barry A. Franklin, Sverre Bergh, Håvard Skjellegrind, Robert E. Sallis, Ingunn Bosnes, Eystein Stordal, Maryam Ziaei, Stian Lydersen, Asgeir Kobro-Flatmoen, Aleksi M. Huuha Javaid Nauman and Ulrik Wisløff

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