Forskningsartikler - Nasjonalt senter for aldring og helse

The Journal of Clinical Investigation, 2022

Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip fracture patients

Abstract

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 mechanism underlying delirium, particularly in relation to the KP, remain elusive.

Methods: We undertook a multi-center 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 one-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, as well as 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 one-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.

Forfattere

Leiv Otto Watne, Christian Thomas Pollmann, Bjorn 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 Fei Fang, Marius Myrstad, Lasse M Giil

Tilgang til artikkelen

Journal of Alzheimer's Disease, 2022

The CERAD Word List Memory Test: Normative Data Based on a Norwegian Population-Based Sample of Healthy Older Adults 70 Years and Above. The HUNT Study

Abstract

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).

Forfattere

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

Tilgang til artikkelen

BMC Public Health, 2022

Public knowledge about dementia risk reduction in Norway

Abstract

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.

Forfattere

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

Tilgang til artikkelen

Journal of Aging and Health, 2022

Marital Histories and Associations With Later-Life Dementia and Mild Cognitive Impairment Risk in the HUNT4 70+ Study in Norway

Abstract

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.

Forfattere

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

Tilgang til artikkelen

Journal of Intellectual & Developmental Disability, 2022

Use of health and dental care services in adults with intellectual disability in relation to age and intellectual disability levels

Abstract

Background: This study investigates the use of health and dental care services in adults with intellectual disability in the last 12 months according to Norwegian recommendations and in relation to age and intellectual disability levels.

Method: A cross-sectional community-based survey including 214 participants (56% men). POMONA health indicators were used for data collection.

Results:
Health checks and contact with general practitioners in the last year increased with age but were less frequent in those with more severe intellectual disability. Hospital admissions were age independent. Less than one-fifth of women had undergone cancer screening, with small variations according to intellectual disability severity levels. Few had an individual plan. More than one-third experienced poor dental health despite frequent controls.
Conclusions: The use of health checks was lower than recommended, especially in individuals with more severe intellectual disability. Service access and individual plan use need to be enhanced, and dental care services should be improved.

Forfattere

Monica Isabel Olsen, Erik Søndenaa, Ellen Melbye Langballe, Marianne Berg Halvorsen, Per Wilhelmsen, Erik Bautz-Holter & Audny Anke

Tilgang til artikkelen

BMC Geriatrics, 2022

Physical performance in older age by sex and educational level: the HUNT Study

Abstract

Background: Population-based studies on physical performance provide important information on older people’s health but rarely include the oldest and least-healthy segment of the population. The aim of this study was to provide representative estimates of physical performance by age, sex, and educational level based on recent data from a population-based health study in Norway that includes older people with a wide range in age and function.

Methods: In the fourth wave of the Trøndelag Health Study (2017-2019), all participants aged 70 + were invited to an additional examination of physical performance assessed by the Short Physical Performance Battery (SPPB), either by attending a testing station or by visits from ambulatory teams. The distribution and variation in SPPB total and subscores, as well as gait speed, are presented by sex, age, and educational level.

Results: The SPPB was registered in 11,394 individuals; 54.8% were women; the age range was 70-105.4 years, with 1,891 persons aged 85 + . SPPB scores decreased by 0.27 points (men) and 0.33 points (women) for each year of age, and gait speed by 0.02 m/sec (men) and 0.03 m/sec (women). Using a frailty cut-off for gait speed at < 0.8 m/sec, the proportion of participants categorized as frail increased from 13.9% in the 70-74 years cohort to 73.9% in participants aged 85 + . Level of education [Formula: see text] 10 years corresponded to 6 years (men) and 4 years (women) earlier onset of frailty (SPPB [Formula: see text] 9) compared to education [Formula: see text] 14 years.

Conclusion: We found that the SPPB captured a gradual decline and wide distribution in physical performance in old age. The results provide information about physical performance, health status, and risk profiles at a population level and can serve as reference data for clinicians, researchers, and healthcare planners.

Forfattere

Kjerstin N. Melsæter, Gro G. Tangen, Håvard K. Skjellegrind, Beatrix Vereijken, Bjørn H. Strand and Pernille Thingstad

Tilgang til artikkelen

Neurology, 2022

Spatial Navigation and Its Association With Biomarkers and Future Dementia in Memory Clinic Patients Without Dementia

Abstract

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.

Forfattere

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

Tilgang til artikkelen

Nursing Ethics

Nurses’ ethical challenges when providing care in nursing homes during the COVID-19 pandemic

Abstract

Background: Older, frail patients with multimorbidity are at an especially high risk for disease severity and death from COVID-19. The social restrictions proved challenging for the residents, their relatives, and the care staff. While these restrictions clearly impacted daily life in Norwegian nursing homes, knowledge about how the pandemic influenced nursing practice is sparse.

Aim: The aim of the study was to illuminate ethical difficult situations experienced by Norwegian nurses working in nursing homes during the COVID-19 pandemic.

Research design and participants: The research design involved semistructured individual interviews conducted with 15 nurses working in 8 nursing homes in 3 health regions in Norway, within both urban and rural areas. Ethical considerations: Oral and written information about the study was provided before the participants gave their written consent. The transcribed interviews were de-identified. The study was approved by the Norwegian Centre for Research Data.

Findings: Four ethical difficult situations were identified: (a) turning the nursing home into a prison; (b) using medication to maintain peace and order; (c) being left alone with the responsibility; and (d) s. impact on decision-making.

Conclusions: The nurses’ ethical challenges were intertwined with external factors, such as national and local guidelines, and the nurses’ own internalized factors, which were connected to their subjective professionality. This duality inflicted emotional distress and gave nurses few opportunities to perform nursing in a professionally sound and safe manner.

Forfattere

Hillestad, A.H., Rokstad, A.M.M., Tretteteig, S., Julnes S.G., Lichtwarck, B. & Eriksen, S.

Tilgang til artikkelen

Journal of Geriatric Oncology, 2022

Geriatric impairments are associated with reduced quality of life and physical function in older patients with cancer receiving radiotherapy – A prospective observational study

Abstract

Introduction
Quality of life (QoL) and function are important outcomes for older adults with cancer. We aimed to assess differences in trends in patient-reported outcomes (PROs) during radiotherapy (RT) between (1) groups with curative or palliative treatment intent and (2) groups defined according to the number of geriatric impairments.
Materials and Methods
A prospective observational study including patients aged ≥65 years receiving curative or palliative RT was conducted. Geriatric assessment (GA) was performed before RT, and cut-offs for impairments within each domain were defined. Patients were grouped according to the number of geriatric impairments: 0, 1, 2, 3, and ≥ 4. Our primary outcomes, global QoL and physical function (PF), were assessed by The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC) (QLQ-C30) at baseline, RT completion, and two, eight, and sixteen weeks later. Differences in trends in outcomes between the groups were assessed by linear mixed models.
Results
301 patients were enrolled, mean age was 73.6 years, 53.8% received curative RT. Patients receiving palliative RT reported significantly worse global QoL and PF compared to the curative group. The prevalence of 0, 1, 2, 3 and ≥ 4 geriatric impairments was 16.6%, 22.7%, 16.9%, 16.3% and 27.5%, respectively. Global QoL and PF gradually decreased with an increasing number of impairments. These group differences remained stable from baseline throughout follow-up without any clinically significant changes for any of the outcomes.
Discussion
Increasing number of geriatric impairments had a profound negative impact on global QoL and PF, but no further decline was observed for any group or outcome, indicating that RT was mainly well tolerated. Thus, geriatric impairments per se should not be reasons for withholding RT. GA is key to identifying vulnerable patients in need of supportive measures, which may have the potential to improve treatment tolerance.

Forfattere

Guro Falk Eriksen, Jūratė Šaltytė Benth, Bjørn Henning Grønberg, Siri Rostoft, Lene Kirkhus, Øyvind Kirkevold, Line Merethe Oldervoll, Asta Bye, Anne Hjelstuen, Marit Slaaen

Tilgang til artikkelen