Forskningsartikler

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

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

Background: Genome-wide Association Studies (GWAS) have reshaped our understanding of the genetic bases of complex diseases in general and neurodegenerative diseases in particular. Despite being a common disorder, dementia with Lewy bodies (DLB), which, together with Parkinson’s disease dementia (PDD), comprise the umbrella term Lewy body dementias (LBD), is far from being well-characterized genetically. This is primarily due to a lack of familial cases and difficulty recruiting large, deeply characterized cohorts, given the high rate of misdiagnosis. By performing the largest GWAS in DLB, we aimed to identify novel risk loci to gain a better understanding of this disease’s pathobiology. Methods: Here, we conducted the largest meta-analysis of genome-wide association studies performed in LBD, using a total of 5,119 cases and 20,988 controls, from five independent datasets, aggregating all previously published DLB genome-wide association results to date, as well as two previously undescribed cohorts. Additionally, we performed a sex stratified GWAS using the discovery datasets. We updated the heritability estimates for DLB and, to fine map these estimates, we used local heritability analysis. We calculated genetic correlation estimates between DLB and a range of other diseases and traits to identify potential pleiotropy. We also performed gene-set analysis to identify genes with excess burden of rare variability and pathway analysis. Lastly, we used the UK Biobank data to perform a PheWas using individuals at the extremes of genetic risk for DLB. Findings: Between November 2018 and September 2022 we analyzed 8.6 million single nucleotide polymorphisms in 3293 DLB cases, 1826 LBD cases and 20,988 controls, as well as phenotypes from the UK Biobank dataset. Despite more than doubling the sample size from the previous GWAS in DLB, we did not identify significant loci in addition to those previously reported at GBA, SNCA, STX1B, and APOE. However, the sex-stratified analysis revealed that the GBA and SNCA signals are mainly driven by males, suggesting a sex-specific genetic architecture of disease. Using only clinical and neuropathologically diagnosed cases, we highlight four loci surpassing the significance threshold. Using the largest cohort of DLB we update our heritability estimates to 13% and fine map these results highlighting regions of the genome with high heritability but no genome-wide significant result so far. Interpretation: These data provide the most comprehensive analysis of genetic variability in DLB to date. The fact that no novel risk loci have been identified after doubling the cohort size indicates the potentially significant role of rare variants in the genetic architecture of DLB and stresses the urgent need for larger, well-characterized cohorts of this disease for genetic studies. The sex-stratified analysis shows that males and females have different signatures of genetic risk for DLB. These results have widespread implications for clinical practice and clinical trials’ design in DLB.

Elizabeth Gibbons, Arvid Rongve, Itziar de Rojas, Alexey Shadrin, Kaitlyn Westra, Allison Baumgartner, Levi Rosendall, Zachary Madaj, Dena G. Hernandez, Owen A. Ross, Valentina Escott-Price, Claire Shepherd, Laura Parkkinen, Sonja W. Scholz, Juan C. Troncoso, Olga Pletnikova, Ted Dawson, Liana Rosenthal, Olaf Ansorge,…Geir Selbæk…Jose Bras

Background:
Nursing home (NH) residents are in their last phase of life, and two aims of the NH’s medical care in Norway is to prevent unnecessary hospital admissions that would not benefit the resident and to facilitate a peaceful death in familiar surroundings when the time comes. However, little is known about the share of residents dying in NHs and the causes of death. We therefore evaluated the cause and place of death in a cohort of NH residents followed from the time of NH admission until death.

Methods:
NH residents were followed from admission to the NH and over the entire course of their NH stay. Demographic and clinical data were collected. Cause and place of death were retrieved from the Norwegian Cause of Death Registry.

Results:
Of 1283 residents, 6.2% died in hospital and 91.2% in a NH. Those who died in hospitals were more often male, died sooner after NH admission, had a less severe degree of dementia and had poorer general health. Dementia was the most common underlying cause of death, followed by cardiovascular disease.

Conclusions:
Dementia is one of the main causes of death in NH residents. In addition, our findings indicate a low number of inappropriate referrals to hospital during the last stage of life. However, further research should explore whether the terminal phase of NH residents is formed in accordance with their preferences and whether appropriate palliative care is offered.

Corinna Vossius, Sverre Bergh, Geir Selbæk, Bjørn Lichtwarck and Janne Myhre

Background:
The CERAD Word List Memory Test (WLMT) is widely used in the assessment of older adults with suspected dementia. Although normative data of the WLMT exist in many different regions of the world, normative data based on large population-based cohorts from the Scandinavian countries are lacking.
Objective: To develop normative data for the WLMT based on a large population-based Norwegian sample of healthy older adults aged 70 years and above, stratified by age, gender, and education.
Methods: A total of 6,356 older adults from two population-based studies in Norway, HUNT4 70 + and HUNT4 Trondheim 70+, were administered the WLMT. Only persons with normal cognitive function were included. We excluded persons with a diagnosis of mild cognitive impairment (MCI) and dementia, and persons with a history of stroke and/or depression. This resulted in 3,951 persons aged between 70 and 90 years, of whom 56.2% were females. Regression-based normative data were developed for this sample.
Results: Age, gender, and education were significant predictors of performance on the WLMT list-learning subtests and the delayed recall subtest, i.e., participants of younger age, female sex, and higher education level attained higher scores compared to participants of older age, male sex, and lower level of education.
Conclusion: Regression-based normative data from the WMLT, stratified by age, gender, and education from a large population-based Norwegian sample of cognitively healthy older adults aged 70 to 90 years are presented. An online norm calculator is available to facilitate scoring of the subtests (in percentiles and z-scores).

Jørgen Wagle, Geir Selbæk, Jratėaltytė Benth, Linda Gjøra, Thale Kinne Rønqvist, Peter Bekkhus-Wetterberg, Karin Persson, Knut Engedal

Background: Several modifiable lifestyle risk factors for dementia have been identified, but it is unclear how much the Norwegian public knows about the relationship between lifestyle and brain health. Therefore, this study aimed to investigate knowledge about modifiable dementia risk and protective factors and beliefs and attitudes towards dementia and dementia risk reduction in a randomly selected subsample of the Norwegian population.
Methods: The total sample (n = 1435) included individuals aged 40-70 years from four counties (Oslo, Innlandet, Nordland and Trøndelag) in Norway. Two online questionnaires were used to measure (1) awareness about dementia risk reduction and (2) an individual`s motivation to change behaviour for dementia risk reduction (MOCHAD-10).
Results: Of the participants, 70% were aware of the potential of dementia risk reduction in general. Physical inactivity (86%), cognitive inactivity (84%) and social isolation (80%) were the most frequently recognised dementia risk factors. On the other hand, diabetes (26%), coronary heart disease (19%), hearing loss (18%) and chronic kidney disease (7%) were less often recognised as dementia risk factors. Comparing men and women, the only significant difference was that women were more likely to report parents with dementia as a risk factor compared to men. Gender, age and educational differences were seen in beliefs and attitudes towards dementia prevention:women reported more negative feelings and attitudes towards dementia than men;those aged 40-49 years – more likely than older age groups – reported that ‘knowing family members with dementia’ or ‘having risk factors’ made them believe they had to change their lifestyle and behaviour.
Conclusions: The results indicate that 70% of the Norwegian public are aware of the potential for dementia risk reduction in general. However, there are major gaps in existing knowledge, particularly for cardiovascular risk factors such as hypertension, coronary heart disease, hypercholesterolemia and metabolic factors (diabetes, obesity). These findings underline the importance of further informing the Norwegian public about lifestyle-related risk and protective factors of dementia. Differences in beliefs and attitudes towards dementia risk prevention by age, gender and education require tailored public risk reduction interventions.

Grete Kjelvik, Anne Marie Mork Rokstad, Josephine Stuebs, Pernille Thingstad, Kay Deckers, Sebastian Köhler, Geir Selbæk

Objectives: Earlier studies suggest that being married in later life protects against dementia, and that being single in old age increases the risk of dementia. In this study, we examine midlife marital status trajectories and their association with dementia and mild cognitive impairment (MCI) at ages 70 plus using a large population based sample from Norway.
Methods: Based on a general population sample linked to population registries (N = 8706), we used multinomial logistic regression to examine the associations between six types of marital trajectories (unmarried, continuously divorced, intermittently divorced, widowed, continuously married, intermittently married) between age 44 and 68 years from national registries and a clinical dementia or a MCI diagnosis after age 70. We estimated relative risk ratios (RRR) and used mediation analyses adjusting for education, number of children, smoking, hypertension, obesity, physical inactivity, diabetes, mental distress, and having no close friends in midlife. Inverse probability weighting and multiple imputations were applied. The population attributable fraction was estimated to assess the potential reduction in dementia cases due to marital histories.
Results: Overall, 11.6% of the participants were diagnosed with dementia and 35.3% with MCI. Dementia prevalence was lowest among the continuously married (11.2%). Adjusting for confounders, the risk of dementia was higher for the unmarried (RRR = 1.73; 95% CI: 1.24, 2.40), continuously divorced (RRR = 1.66; 95% CI: 1.14, 2.43), and intermittently divorced (RRR = 1.50; 95% CI: 1.09, 2.06) compared to the continuously married. In general, marital trajectory was less associated with MCI than with dementia. In the counterfactual scenario, where all participants had the same risk of receiving a dementia diagnosis as the continuously married group, there would be 6.0% fewer dementia cases.
Discussion: Our data confirm that staying married in midlife is associated with a lower risk of dementia and that divorced people account for a substantial share of dementia cases.

Vegard Skirbekk, Catherine E Bowen, Asta Håberg, Astanand Jugessur, Bo Engdahl, Bernt Bratsberg, Ekaterina Zotcheva, Geir Selbæk, Hans-Peter Kohler, Jordan Weiss, Jennifer R Harris, Sarah E Tom, Steinar Krokstad, Yaakov Stern, Bjørn Heine Strand

Background and objectives: Impaired spatial navigation is considered an early sign in many neurodegenerative diseases. We aimed to determine if spatial navigation was associated with future dementia in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI), and to explore associations between spatial navigation and biomarkers of Alzheimer’s disease (AD) and neurodegeneration.

Methods: The study included memory clinic patients without dementia in the longitudinal BioFINDER cohort. The Floor Maze Test (FMT) was used to assess spatial navigation at baseline. Conversion to dementia were evaluated at 2- and 4-year follow-ups. At baseline, amyloid-β 42/40 ratio, phosphorylated-tau (p-tau) and neurofilament light (NfL) were analysed in CSF. Cortical thickness and volume of regions relevant for navigation, and white matter lesion volume were quantified from MRI. The predictive role of the FMT for conversion to all-cause dementia was analysed using logistic regression analyses in two models; 1) controlled for age, sex and education, and 2) adding baseline cognitive status and MMSE. Associations between FMT and biomarkers were adjusted for age, sex, and cognitive status (SCD or MCI).

Results: 156 patients with SCD and 176 patients with MCI were included. FMT total time was associated with progression to all-cause dementia in model 2 at 2-year (OR 1.10, 95% CI 1.04, 1.16) and at 4-year follow-up (OR 1.10, 95% CI 1.04, 1.16), i.e., a 10 % increase in odds of developing dementia per every 10 sec increase in FMT. In the adjusted analyses, P-tau and NfL was associated with FMT total time, as well as hippocampal volume, parahippocampal and inferior parietal cortical thickness. Amyloid-β 42/40 ratio was not associated with FMT total time.

Discussion: Impaired spatial navigation was associated with conversion to dementia within 2 and 4 years, and with key CSF and MRI biomarkers for AD and neurodegeneration in patients with SCD and MCI. This supports its use in early cognitive assessments, but the predictive accuracy should be validated in other cohorts.

Classification of evidence: This is a Class 1 prospective cohort study demonstrating association of baseline markers of spatial recognition with development of dementia in patients with SCD or MCI at baseline.

Gro Gujord Tangen, Maria H Nilsson, Erik Stomrud, Sebastian Palmqvist, Oskar Hansson

Objectives: Neuropsychiatric symptoms (NPS) are associated with dementia severity and progression rate. NPS clusters have different neurobiological underpinnings; therefore, their effect on dementia progression may differ. Further, little is known about whether individual comorbidities affect progression rate. We investigated the effect of NPS clusters and individual comorbidities on dementia progression.
Methods: A memory clinic cohort with all-cause dementia (N = 442), was followed for up to three years from diagnosis. Previously, we found trajectory groups of dementia progression in this cohort: one with slow progression and two with rapid progression. In the present study, using principal component analysis, three symptom clusters of NPS were on the Neuropsychiatric Inventory Questionnaire (NPI-Q): agitation, affective, and psychosis symptom clusters. Data regarding comorbidity were collected by linkage to the Norwegian patient registry. Multinomial logistic regression was applied to explore the association between NPS clusters and comorbidity with trajectory-group membership.
Results: Adjusted for demographics, dementia aetiology, comorbidity, and cognition, we found that, at the time of dementia diagnosis, for every point within the psychosis symptom cluster of the NPI-Q, the risk of rapid progression increased by 53%; for every point within the affective symptom cluster, the risk of rapid progression increased by 29%. A previous diagnosis of mental and behavioural disorders (excluding dementia) decreased the risk of rapid dementia progression by 65%.
Conclusions: Psychosis and affective symptom clusters at the time of diagnosis were associated with rapid progression of dementia. Previous diagnoses of mental and behavioural disorders (excluding dementia) were associated with slow progression. This article is protected by copyright. All rights reserved.

Trine Holt Edwin, Bjørn Heine Strand, Karin Persson, Knut Engedal, Geir Selbæk, Anne-Brita Knapskog.