Forskningsartikler

Abstarct: 

We examined associations between body mass index (BMI), waist circumference (WC), and dementia risk, and differences in BMI and WC trajectories before dementia diagnosis. We included 9,739 participants (54% women) aged 70+ from the Trøndelag Health Study (HUNT4 70+). BMI was measured four times (1984-2019) and WC three times (1995-2019). Dementia diagnoses were clinically assessed at HUNT4 70+ . Women and men with dementia had higher midlife BMI and WC than those without dementia. These differences diminished closer to diagnosis, especially in women. Midlife obesity in both sexes and midlife overweight, high WC, and overweight/obesity with high WC in men were linked to higher dementia risk. Lower dementia risk was observed with late-life overweight for both sexes, late-life high WC in women, late-life overweight/obesity with normal WC in men or high WC in women. Adiposity measures and their changes influence dementia risk differently in women and men.

Ekaterina Zotcheva, Bjørn Heine Strand, Vegard Skirbekk, Kay Deckers, Steinar Krokstad, Gill Livingston, Archana Singh-Manoux, Geir Selbæk

Abstract

Aims: To describe: (i) Experiences of older patients with cancer after receiving an intervention based on geriatric assessment with management. (ii) Experiences of cancer nurses in municipal health care from implementing an intervention based on geriatric assessment with management and their perspectives on the intervention.

Design: A qualitative, descriptive interview study reported according to COREQ.

Methods: The sample comprises five men and three women with cancer, mean age 75 years, and 11 female cancer nurses. Data collection was performed as individual patient interviews, and individual and small group interviews with cancer nurses. Inductive, thematic analysis was performed.

Results: Three main themes were generated: Systematic approach, Patient-centeredness and Regular and professional contact.

Patient or public contribution: Participants did not review transcripts, participate in analysis, or review results. This was not deemed appropriate, as all interviews were analysed as a whole. User representatives participated in the planning and conducting of the intervention study and implementation procedures.

Trial registration: ClinicalTrials.gov Identifier: NCT03881137.

May Ingvild Volungholen Sollid, Line Melby, Marit Slaaen, Grethe Eilertsen, Inga Marie Røyset, Øyvind Kirkevold

Abstarct:

Despite a well-known inverse association between education and dementia risk, the mediating mechanisms are not well understood. We explored how lifestyle and health risk factors across the life-course mediate the relationship between education and dementia among adults aged 70 + years. We included 7,655 participants with dementia diagnoses and education information, using a historical cohort design linking prospective exposure data across the life course from the HUNT4 70 + Study with registry data from Statistics Norway and earlier HUNT surveys. We conducted causal mediation analysis to assess the mediating roles of occupational characteristics, lifestyle factors (smoking, physical inactivity), and health risk factors (obesity, hypertension, diabetes, hearing impairment, cardiovascular diseases, LDL cholesterol, depression, anxiety) assessed during early, middle, and late adulthood in the relationship between education and dementia in later life. Participants with lower education were more likely to have dementia with odds ratios of 1.99, 1.88, 1.83 for the model’s accounting exposure to mediators during early, middle, and late adulthood, respectively. These associations were partially mediated by the joint effect of health and lifestyle risk factors from early through late adulthood (mediated 11.55-19.50%). Health risk factors from early to late adulthood jointly mediated 6.85-13.06% of the effect of low education on dementia risk later in life. Additionally, lifestyle factors during middle and late adulthood jointly mediated 4.11-4.96% of the total effect of low education on dementia risk later in life. Educational differences in dementia risk can partly mediated by lifestyle and health factors across the life course. These findings suggest potential targets to address varying dementia risks linked to education levels.

Teferi Mekonnen, Vegard Skirbekk, Asta Kristine Håberg, Bo Engdahl, Ekaterina Zotcheva, Astanand Jugessur, Catherine Bowen, Geir Selbaek, Hans-Peter Kohler, Jennifer R Harris, Sarah E Tom, Steinar Krokstad, Trine Holt Edwin, Dana Kristjansson, Merete Ellingjord-Dale, Yaakov Stern, Bernt Bratsberg, Bjørn Heine Strand

Abstract

Background: With the anticipated increase in dementia prevalence over the coming decade, understanding the experience of receiving a dementia diagnosis for people living with cognitive impairment remains limited. This study aims to explore the implications of a family member with cognitive impairment receiving a dementia diagnosis or not from the perspective of their next of kin.

Methods: A qualitative descriptive design was applied using individual interviews for data collection. Participants were recruited based on the cognitive function level of their family members, which was compatible with dementia as assessed with the Montreal Cognitive Assessment Scale (MoCA). The sample consisted of eight participants, comprising family members of five individuals with confirmed dementia diagnoses and three undiagnosed. The analysis was performed using four steps of systematic text condensation to discern codes, categories, and the overarching theme.

Results: Three main categories were created: (1) Impact of observed cognitive decline, (2) Impact of diagnosis on service engagement, and (3) Support and follow-up for family caregivers. The findings show that next of kin who have received a dementia diagnosis for their family members are more proactive in seeking help and services, are better informed about available resources, and are more concerned about future challenges. On the other hand, next of kin to family members without a diagnosis are more inclined to handle the situation on their own, have less access to information and services, and generally express less concern about future problems.

Conclusion: The study reveals the benefits of receiving a timely dementia diagnosis in shaping more effective support systems and policies. This ensures that the next of kin and the person with cognitive impairment can navigate the complexities of dementia with greater confidence and preparedness, thereby enhancing their quality of life.

Inger Molvik, Grete Kjelvik, Geir Selbæk & Anne Marie Mork Rokstad

Abstract:

Werner syndrome (WS), caused by mutations in the RecQ helicase WERNER (WRN) gene, is a classical accelerated aging disease with patients suffering from several metabolic dysfunctions without a cure. While, as we previously reported, depleted NAD+ causes accumulation of damaged mitochondria, leading to compromised metabolism, how mitochondrial NAD+ changes in WS and the impact on WS pathologies were unknown. We show that loss of WRN increases senescence in mesenchymal stem cells (MSCs) likely related to dysregulation of metabolic and aging pathways. In line with this, NAD+ augmentation, via supplementation with nicotinamide riboside, reduces senescence and improves mitochondrial metabolic profiles in MSCs with WRN knockout (WRN-/-) and in primary fibroblasts derived from WS patients compared to controls. Moreover, WRN deficiency results in decreased mitochondrial NAD+ (measured indirectly via mitochondrially-expressed PARP activity), and altered expression of key salvage pathway enzymes, including NMNAT1 and NAMPT; ChIP-seq data analysis unveils a potential co-regulatory axis between WRN and the NMNATs, likely important for chromatin stability and DNA metabolism. However, restoration of mitochondrial or cellular NAD+ is not sufficient to reinstall cellular proliferation in immortalized cells with siRNA-mediated knockdown of WRN, highlighting an indispensable role of WRN in proliferation even in an NAD+ affluent environment. Further cell and animal studies are needed to deepen our understanding of the underlying mechanisms, facilitating related drug development.

Sofie Lautrup, Shi-Qi Zhang, Shinichiro Funayama, Lisa Lirussi, Tina Visnovska, Hoi-Hung Cheung, Marc Niere, Yuyao Tian, Hilde Loge Nilsen, Geir Selbæk, Janna Saarela, Yoshiro Maezawa, Koutaro Yokote, Per Nilsson, Wai-Yee Chan, Hisaya Kato, Mathias Ziegler, Vilhelm A Bohr & Evandro F Fang

Abstract

INTRODUCTION: The Cambridge Cognitive Examination modified for use in peo[1]ple with Down syndrome (CAMCOG-DS) is a sensitive cognitive test for Alzheimer’s disease (AD)–related decline in people with DS, but needs updates for sensitivity, cul[1]tural adaptability, and additional memory/executive function items. This study aimed to develop and validate the CAMCOG-DS-II.

METHODS: In this multi-language, multi-site study, the psychometric properties of the CAMCOG-DS-II were evaluated against previously validated measures in 223 participants (mean age: 40.18 years) with DS across seven countries.

RESULTS: The CAMCOG-DS-II had a high completion rate, minimal floor/ceiling effects (compared to the modified Cued Recall Test, the CANTAB Paired Associates Learning, and the Purdue Pegboard), strong validity and reliability, and performance was unaf[1]fected by language across sites. It differentiated between those with/without AD and distinguished clinically rated cognitively stable and prodromal individuals.

CONCLUSION: The CAMCOG-DS-II is a sensitive measure of cognitive performance in people with DS at risk of AD. Its cross-language and site reliability support its potential use in AD–DS clinical trials.

Phoebe Ivain, Asaad Baksh, Fedal Saini, Mina Idris, Miren Tamayo-Elizalde, Jasmine Wells, Bessy Benejam, Sandra Virginia Loosli, Katja Sandkühler, Elisabeth Wlasich, Olivia Wagemann, Johannes Levin, Diane Martet, Silvia Sacco, Ségolène Falquero, Manon Clert, Anne-Sophie Rebillat, Wan Ming Khoo, Madelaine Amelia Smith, Jessica Beresford-Webb, Shahid Zaman, María Carmona-Iragui, Laura Videla, Juan Fortea, Ellen Melbye Langballe, Ingrid Tøndel Medbøen, Frode Kibsgaard Larsen, Eleni Baldimtsi, Raphaella Paradisi, Panagiotis Ntailakis, Magdalini Tsolaki, Georgia Papantoniou, Eimear McGlinchey, Mary McCarron, Seán Kennelly & André Strydom

Abstract:
Introduction: We investigated the effectiveness of the multicomponent learning, innovation, volunteer support, empowerment (LIVE) intervention on caregiver burden and care time in dyads of home-dwelling people with dementia and caregivers.

Method: A 24 month, multicenter, stepped-wedge trial, randomized dyads to receive the 6-month LIVE intervention by municipal coordinators (May 2019 to December 2021). Primary outcomes were caregiver burden assessed by Relative Stress Scale (RSS) and informal care time spent on personal activities assessed by Resource Utilization in Dementia Personal Activities of Daily Living (RUD-PADL). Analyses used an intention-to-treat.

Results: Two hundred eighty dyads were enrolled. Caregivers during the intervention period reported lower levels of RSS of 0.7 points (standard deviation [SD]: 0.8) compared to the caregivers in the control period. Caregivers during the intervention period reported more time spent on PADL of 11.7 hours/month (SD: 8.7) compared to caregivers during the control period; both were not statistically significant (P > 0.05).

Discussion: The LIVE intervention did not reduce caregiver burden or care time.

Trial registration: ClinicalTrials.gov NCT04043364.

Highlights: Two hundred eighty persons with dementia and caregivers were included in a stepped wedge randomized controlled trial. We used the learning, innovation, volunteer support, empowerment (LIVE) intervention. The LIVE intervention did not reduce caregiver burden or informal care time. The LIVE intervention improved the caregiver’s clinical global impression of change. Positive change was most pronounced for coordinator personalized support.

Line Iden Berge, Renira Corinne Angeles, Marie Hidle Gedde, Stein Erik Fæø, Janne Mannseth, Maarja Vislapuu, Natalie Genevieve Søyland Puaschitz, Eirin Hillestad, Dag Aarsland, Wilco Peter Achterberg, Heather Allore, Clive Ballard, Fan Li, Geir Selbæk, Ipsit Vihang Vahia & Bettina Sandgate Husebo

Abstract:
Background:
This study forecasts total and cause-specific health expenditures in Norway to 2050 and quantifies the contribution of four key drivers—total population growth, population aging, changes in disease prevalence, and cost per case—on future health care spending.

Methods:
We forecast spending for 116 health conditions in Norway from 2022 to 2050, using historical and forecasted data of population growth, disease prevalence, gross domestic product (GDP), health spending, and residual factors. Our analysis included a reference scenario that forecasted disease-specific health spending; two alternative scenarios examining the effects of alternative unit cost developments; and a scenario examining the consequences of improved behavioral and metabolic risk factors.

Results:
Health spending increased from 10.6% (95% uncertainty interval, 10.2–11.1) of GDP in 2022 to 14.3% (13.0–15.7) in 2050 in the reference scenario. Among the top aggregate causes of Norwegian health spending in 2022, the spending for neurological disorders rose the most, from 1.7% (1.6–1.8) to 2.7% (2.3–3.1) of GDP, surpassing mental and substance use disorders which rose from 2.2% (2.1–2.3) to 2.4% (2.2–2.6) of GDP. Of the 116 single conditions analyzed, dementias accounted for the highest spending in 2022. This expenditure was forecasted to increase considerably from 1.1% (1.09–1.2) to 1.9% (1.6–2.2) of GDP by 2050, largely due to population aging. Spending on other old-age-related conditions like falls, stroke, and diabetes, was also forecasted to increase. Increased population, aging, and spending per case contributed to increased future spending. Reduced behavioral and metabolic risks were forecasted to increase the number of elderly persons and reduce age-specific disease prevalence but had little impact on forecasted health spending.

Conclusions:
Health spending growth was forecasted regardless of the scenario, and Norway needs to plan for this. However, policymakers can curb total spending growth, while maintaining health care quality and output, by ensuring more efficient allocation and effective use of resources. While the overall impact of behavioral and metabolic risk reductions on total healthcare spending was modest, reducing risk factors is needed if countries aim to achieve a healthier, longer-living population.

Jonas Minet Kinge, Henning Øien, Joseph L. Dieleman, Bjørn-Atle Reme, Ann Kristin Skrindo Knudsen, Geir Godager, Geir Selbæk, Jan C. Frich, Enis Barış, Christopher J. L. Murray & Stein Emil Vollset

Abstract:

Introduction: Understanding factors that influence care service use is crucial for developing preventive strategies to maintain independence among older adults. In this study, we aimed to identify distinct trajectory groups of municipal care service use among community-dwelling older adults to determine whether daily physical activity is associated with future care service use.

Methods: This prospective cohort study included 981 community-dwelling older adults from the HUNT4 Trondheim 70+ study. At baseline, physical activity was assessed over seven consecutive days using two accelerometers attached to the thigh and lower back. An activity type machine learning model was used to classify the physical activity types: walking, standing, cycling, running, sitting, and lying. Municipal care service use was retrieved monthly from medical records for 3 years. Using group-based trajectory modeling, we identified distinct trajectories of care service use. Multinomial regression models adjusted for age, sex, education level, dementia, and physical performance were used to evaluate the associations between daily physical activity at baseline and care service group belonging.

Results: We identified four distinct trajectory groups of municipal care service use, labeled steady low (72.7%), low increasing (9.0%), medium increasing (12.0%), and high increasing (6.3%). Daily time spent in total physical activity was not associated with trajectory group belonging when adjusted for age, sex, education level, dementia, and physical performance. However, more time spent walking, in bouts lasting longer than a minute, was associated with a reduced relative risk of belonging to the high increasing compared to the steady low group. Furthermore, age, physical performance, and dementia were all significantly associated with trajectory group belonging, and sex differences were observed. Compared to women, men had a reduced relative risk of belonging to the low increasing, medium increasing, or high increasing trajectory groups.

Conclusion: This study identified four distinct trajectories of municipal care service use among older adults over 3 years. Total daily physical activity was not associated with trajectories of care service use, but more time spent walking in longer bouts was independently associated with lower care service use, even when adjusted for the strong predictors of physical performance, dementia diagnosis, and age.

Astrid Ustad, Trine Holt Edwin, Kjerstin Næss Melsæter, Karen Sverdrup, Gro Gujord Tangen, Øystein Døhl, Pernille Thingstad, Beatrix Vereijken and Nina Skjæret-Maroni