Forskningsartikler

Background: Aggregation of amyloid-β (Aβ) is an early pathological event in Alzheimer’s disease (AD). Consequently, measures of pathogenic aggregated Aβ are attractive biomarkers for AD. Here, we use a recently developed Thioflavin-T-Fluorescence Correlation Spectroscopy (ThT-FCS) assay to quantify structured ThT-responsive protein aggregates, so-called nanoplaques, in the cerebrospinal fluid (CSF).

Objective: The overall aim of this work was to assess whether ThT-FCS determined CSF nanoplaque levels could predict amyloid brain uptake as determined by 18F-Flutemetamol PET analysis. Further, we assess whether nanoplaque levels could predict clinical AD.

Methods: Nanoplaque levels in the CSF from 54 memory clinic patients were compared between sub-groups classified by 18F-Flutemetamol PET as amyloid-positive or amyloid-negative, and by clinical assessment as AD or non-AD.

Results: Nanoplaque levels did not differ between amyloid groups and could not predict brain amyloid uptake. However, nanoplaque levels were significantly increased in patients with clinical AD, and were significant predictors for AD when adjusting for age, sex, cognitive function, and apolipoprotein E (APOE) genotype.

Conclusion: The concentration of nanoplaques in the CSF differentiates patients with clinical AD from non-AD patients.

Mari Aksnes, Ebba Glersen Müller, Ann Tiiman, Trine Holt Edwin, Lars Terenius, Mona-Elisabeth Revheim, Vladana Vukojević, Nenad Bogdanović, Anne-Brita Knapskog

Bakgrunn: Alkohol og legemidler kan føre til økt funksjonssvikt, sykelighet og død, særlig hos personer med høy samsykelighet. Hensikten med studien var å undersøke bruken av alkohol, tobakk og vanedannende legemidler hos hjemmetjenestemottakere over 60 år i en middels stor kommune og se hvilke faktorer som hadde sammenheng med alkoholbruk.
Metode: Tverrsnittsundersøkelse der 210 personer over 60 år som mottok hjemmebaserte tjenester i en norsk kommune, ble intervjuet om deres bruk av alkohol, tobakk og vanedannende legemidler samt deres psykiske symptomer. Sammenhengen mellom alkoholbruk og andre variabler ble undersøkt.

Resultat: Hver femte deltaker hadde demens, 38 % hadde depressive symptomer, 16 % hadde angstsymptomer, 57 % brukte alkohol, 11 % brukte angstdempende legemidler, og 31 % brukte vanedannende legemidler mot søvnproblemer. Alkoholbruk hadde sammenheng med lavere alder, å røyke tobakk og færre depresjonssymptomer.

Konklusjon: Nesten 60 % brukte alkohol, og alkoholbruken var høyere hos yngre, blant personer som røykte tobakk, og blant deltakere med færre depresjonssymptomer. En av tre brukte vanedannende legemidler mot søvnproblemer. Denne kunnskapen er nyttig for ansatte i hjemmetjenesten og bør påvirke organiseringen tjenestene, hvilke symptomer man skal være oppmerksomme på hos brukerne, og hvilken behandling og oppfølging som skal gis.

Sverre Bergh, Elin Michaelsen, Nina Beate Andfossen, Bjørn Lichtwarck, Geir Selbæk & Øyvind Kirkevold

Abstract
Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.

Douglas P. Wightman, Iris E. Jansen, Jeanne E. Savage, Alexey A. Shadrin, Shahram Bahrami, Dominic Holland, Arvid Rongve, Sigrid Børte, Bendik S. Winsvold, Ole Kristian Drange, Amy E. Martinsen, Anne Heidi Skogholt, Cristen Willer, Geir Bråthen, Ingunn Bosnes, Jonas Bille Nielsen, Lars G. Fritsche, Laurent F. Thomas, Linda M. Pedersen, Maiken E. Gabrielsen, Marianne Bakke Johnsen, Tore Wergeland Meisingset, Wei Zhou, Petroula Proitsi, Angela Hodges, Richard Dobson, Latha Velayudhan, 23andMe Research Team, Julia M. Sealock, Lea K. Davis, Nancy L. Pedersen, Chandra A. Reynolds, Ida K. Karlsson, Sigurdur Magnusson, Hreinn Stefansson, Steinunn Thordardottir, Palmi V. Jonsson, Jon Snaedal, Anna Zettergren, Ingmar Skoog, Silke Kern, Margda Waern, Henrik Zetterberg, Kaj Blennow, Eystein Stordal, Kristian Hveem, John-Anker Zwart, Lavinia Athanasiu, Per Selnes, Ingvild Saltvedt, Sigrid B. Sando, Ingun Ulstein, Srdjan Djurovic, Tormod Fladby, Dag Aarsland, Geir Selbæk, Stephan Ripke, Kari Stefansson, Ole A. Andreassen & Danielle Posthuma

Abstract
Objectives: Relationship quality (RQ) between a person with dementia and a family carer may influence their health and quality of life. However, evidence regarding its course and influencing factors is limited. We aimed to explore RQ trajectories in dementia, and identify predictors of change.
Methods: We analysed longitudinal data from a cohort of 350 community-dwelling people with dementia and their informal carers, participating in the Actifcare study in eight European countries. The Positive Affect Index, rated separately by both people with dementia and their carers, assessed RQ. Other measures included the Neuropsychiatric Inventory Questionnaire (regarding persons with dementia), and the Relative Stress Scale, Sense of Coherence Scale and Lubben Social Network Scale (for carers). Trajectories and influencing factors were explored applying a latent growth model (LGM).
Results: RQ in the group of carers declined over 1 year, but RQ scores for the persons with dementia did not change. Higher stress in carers negatively influenced their baseline RQ ratings. Carer sense of coherence and being a spouse were associated with more positive baseline RQ carer assessments. Higher levels of neuropsychiatric symptoms were linked to decline in carers’ RQ, whereas social support was associated with more positive RQ trajectories.
Conclusion: This study provides a valuable insight into the course of RQ. LGM proved useful to explore the factors that influence RQ trajectories and variability within- and between-persons. Our findings emphasise the importance of carer-perceived social support and sense of coherence, and of reducing neuropsychiatric symptoms, in maintaining a good RQ.

Maria J Marques, Eva Y L Tan, Bob Woods, Hannah Jelley, Liselot Kerpershoek, Louise Hopper, Kate Irving, Anja Bieber, Astrid Stephan, Anders Sköldunger, Britt-Marie Sjölund, Geir Selbæk, Janne Røsvik, Orazio Zanetti, Daniel M Portolani, João Marôco, Marjolein de Vugt, Frans Verhey, Manuel Gonçalves-Pereira, Actifcare Consortium

Abstract: We present associations between neuropsychiatric symptoms (NPS) and brain morphology in a large sample of patients with mild cognitive impairment (MCI) and Alzheimer’s disease with dementia (AD dementia).Several studies assessed NPS factor structure in MCI and AD dementia, but we know of no study that tested for associations between NPS factors and brain morphology. The use of factor scores increases parsimony and power. For transparency, we performed an additional analysis with selected Neuropsychiatric Inventory – Questionnaire (NPI-Q) items. Including regional cortical thickness, cortical and subcortical volumes, we examined associations between NPS and brain morphology across the whole brain in an unbiased fashion. We reported both statistical significance and effect sizes, using linear models adjusted for multiple comparisons by false discovery rate (FDR). Moreover, we included an interaction term for diagnosis and could thereby compare associations of NPS and brain morphology between MCI and AD dementia.We found an association between the factor elation and thicker right anterior cingulate cortex across MCI and AD dementia. Associations between the factors depression to thickness of the banks of the left superior temporal sulcus and psychosis to the left post-central volume depended on diagnosis: in MCI these associations were positive, in AD dementia negative.Our findings indicate that NPS in MCI and AD dementia are not exclusively associated with atrophy and support previous findings of associations between NPS and mainly frontotemporal brain structures.
Objectives: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and Alzheimer’s disease with dementia (AD dementia), but their brain structural correlates are unknown. We tested for associations between NPS and MRI-based cortical and subcortical morphometry in patients with MCI and AD dementia.
Design: Cross-sectional.

Settings: Conducted in Norway.
Participants: Patients with MCI (n = 102) and AD dementia (n = 133) from the Memory Clinic and the Geriatric Psychiatry Unit at Oslo University Hospital.
Measurements: Neuropsychiatric Inventory – Questionnaire (NPI-Q) severity indices were reduced using principal component analysis (PCA) and tested for associations with 170 MRI features using linear models and false discovery rate (FDR) adjustment. We also tested for differences between groups. For transparency, we added analyses with selected NPI-Q items.
Results: PCA revealed four factors: elation, psychosis, depression, and motor behavior.FDR adjustment revealed a significant positive association (B = 0.20, pFDR < 0.005) between elation and thickness of the right caudal anterior cingulate cortex (ACC) across groups, and significant interactions between diagnosis and psychosis (B = −0.48, pFDR < 0.0010) on the left post-central volume and between diagnosis and depression (B = −0.40, pFDR < 0.005) on the thickness of the banks of the left superior temporal sulcus. Associations of apathy, anxiety, and nighttime behavior to the left temporal lobe were replicated.
Conclusions: The positive association between elation and ACC thickness suggests that mechanisms other than atrophy underly elation. Interactions between diagnosis and NPS on MRI features suggest different mechanisms of NPS in our MCI and AD dementia samples. The results contribute to a better understanding of NPS brain mechanisms in MCI and AD dementia.

Nikias Siafarikas, Dag Alnæs, Jennifer Monereo-Sanchez, Martina J Lund, Geir Selbæk, Maria Stylianou-Korsnes, Karin Persson, Maria Lage Barca, Ina Selseth Almdahl, Tormod Fladby, Dag Aarsland, Ole A Andreassen, Lars T Westlye

Abstract:
Purpose: To explore and describe experiences of older patients with cancer throughout their radiotherapy treatment, from diagnosis until follow-up after treatment.

Methods: Individual interviews were conducted to explore different phases of radiotherapy. Interviews were recorded and transcribed verbatim. Inductive content analysis was applied. Each interview was coded separately. Then to the codes were analyzed further, and an overall theme was developed.

Results: Twelve older patients with cancer, (7 male, 5 female) aged ≥ 65 related their experiences from radiotherapy treatment. A main theme describes the essence of their experiences; Understanding “just enough”. The theme comprises five main categories: Understandable, adapted information is crucial for trusting health services; Previous experiences influence patients’ perception and understanding; Involvement of next of kin is crucial to patients’ comprehension; Professional treatment decisions and well-organized treatment determines satisfaction and Experiences of cooperation and coordination of services affects dependability.

Conclusions: Findings from this study describe how understanding “just enough” – not too much nor too little – may assist older patients with cancer in participating in treatment decisions, preventing false beliefs, feeling reassured during treatment and in navigating the complex health care system. Next of kin are important assets for older patients with cancer in understanding “just enough”. Cancer nurses may map comprehension of information, as well as reveal patients’ previous experiences.

May Ingvild Volungholen Sollid, Øyvind Kirkevold, Marit Slaaen, Bente Ervik, Line Melby, Grethe Eilertsen

Introduction:
Depression is common amongst people with dementia. This study examines whether locus of control (LoC), a perceived control construct influential in the coping process, is related to depressive symptoms in this population.
Methods:
In this prospective observational study, 257 community-dwelling older adults with a confirmed dementia diagnosis were included. At baseline, measures of depressive symptoms, LoC, cognition, independent functional ability, general health, dementia severity, and dementia disease insight were collected. At follow-up, measures of depressive symptoms and cognition were collected. Multiple linear regression using degree of depressive symptoms as measured with Montgomery-Asberg Depression Rating Scale as a dependent variable was applied to assess whether LoC was associated with depressive symptoms at baseline and followup while controlling for covariates.
Results:
LoC (p < 0.001), general health (p = 0.003), and insight (p = 0.010) were associated with severity of depressive symptoms at baseline, accounting for 28% of the variance. LoC (p = 0.025) and depressive symptoms (p < 0.001) at baseline were associated with severity of depressive symptoms at follow-up, accounting for 56.3% of the variance.
Conclusion:
LoC was significantly associated with severity of depressive symptoms in people with dementia at baseline and at follow-up. Attention to LoC may be valuable for our understanding of depression in people with dementia, and interventions targeting depression could benefit from including a focus on internalizing perceived control. However, these findings are novel, and more research is needed.

Ingeborg Halse, Guro Hanevold Bjørkløf, Knut Engedal, Geir Selbæk, Maria Lage Barca

Objectives: To explore alcohol consumption among older Norwegian adults with symptoms of cognitive decline, assess the agreement between the reports of older adults and their next of kin regarding a person’s alcohol consumption, and explore clinical and sociodemographic variables associated with agreement.

Method: Alcohol consumption was measured among 3608 older adults consulting specialist health care for symptoms of cognitive decline. Agreement between the participant and their next of kin regarding the participant’s alcohol consumption was assessed with a weighted kappa (κ). A logistic regression analysis for hierarchical data was used to explore variables associated with agreement.
Results: Both the participants and their next of kin reported that more than 20% of the participants consumed alcohol 1-3 times a week, and that approximately 10% consumed alcohol four or more times a week. The agreement between the participant’s and their next of kin’s report regarding the participant’s alcohol consumption was high (κ = .852), and variables associated with agreement were no cognitive decline, not drinking alcohol during the last year or ever as reported by the participant, and low agitation scores on a psychiatric assessment.
Conclusion: This paper found alcohol consumption among older adults with symptoms of cognitive decline that was above the national average in Norway. This is also the first paper to demonstrate that a next of kin can be a reliable source of information regarding older adults’ alcohol consumption. Health personnel should consider these findings when performing medical assessments or developing interventions for older adults.

Ben Kamsvaag, Sverre Bergh, Jūratė Šaltytė Benth, Geir Selbæk, Kjerstin Tevik, Anne-Sofie Helvik

Background: Dementia is one of the main causes of disability and dependence in older people, and people with dementia need comprehensive healthcare services, preferably in their own homes. A well-organized home care service designed for people with dementia is necessary to meet their needs for health- and social care. Therefore, it is important to gain knowledge about how people with dementia experience the home care service and if the service responds to their wishes and needs. The aim of this study was to explore the experience of home care services among people with dementia, to understand the continuity in services, how the service was adapted to people with dementia, and how the patient experienced person-centered care and shared decision-making.

Methods: We used a qualitative, exploratory design based on a phenomenological-hermeneutic approach and performed individual in-depth interviews with persons with dementia. A convenience sample of 12 persons with moderate to severe degrees of dementia from four Norwegian municipalities participated in the study. The interviews were conducted in February 2019.

Results: The findings identified that the participants appreciated the possibility to stay safely in their own homes and mostly experienced good support from staff. They expressed various views and understanding of the service and experienced limited opportunities for user involvement and individualized, tailored service. The overall theme summarizing the findings was: “It is difficult for people with dementia to understand and influence home care services, but the services facilitate the possibility to stay at home and feel safe with support from staff.”

Conclusion: The participants did not fully understand the organization of the care and support they received from the home care services, but they adapted to the service without asking for changes based on their needs or desires. Although person-centered care is recommended both nationally and internationally, the participants experienced little inclusion in defining the service they received, and it was perceived as unclear how they could participate in shared decision-making.

Kari-Anne Hoel, Anne Marie Mork Rokstad, Ingvild Hjorth Feiring, Bjørn Lichtwarck, Geir Selbæk, Sverre Bergh