Forskningsartikler

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

Abstract:
Background: With the increasing number of older adults globally, there is a constant search for new ways to organize health care services. Digital health services are promising and may reduce workload and at the same time improve patient well-being. A certain level of eHealth literacy is needed to be able to use digital health services. However, knowledge of technology readiness in this target group of older adults is unclear.

Objective: The aim of this study was to understand the technology readiness level of a group of older adults who were provided home care services in order to address the present and future needs of this group in relation to the implementation of digital health care services.

Methods: This quantitative cross-sectional study included 149 older adults from Norway receiving home care services. The participants completed the Readiness and Enablement Index for Health Technology (READHY) instrument, assessments of well-being (World Health Organization-Five Well-Being Index [WHO-5]), and assessments of demographic and clinical variables (sex, age, education, living situation, comorbidity, use of digital devices, and use of IT). Cluster analyses were used to group the users according to their technology readiness.

Results: The mean participant age was 78.6 (SD 8.0) years, and 55.7% (83/149) were women. There was good consistency within the assumed READHY scales (Cronbach α=.61-.91). The participants were grouped into 4 clusters, which differed in terms of READHY scores, demographic variables, and the use of IT in daily life. Participants in cluster 1 (n=40) had the highest scores on the READHY scales, were younger, had a larger proportion of men, had higher education, and had better access to digital devices and IT. Participants in cluster 4 (n=16) scored the lowest on eHealth literacy knowledge. Participants in cluster 1 had relatively high levels of eHealth literacy knowledge and were expected to benefit from digital health services, while participants in cluster 4 had the lowest level of eHealth literacy and would not easily be able to start using digital health services.

Conclusions: The technology readiness level varied in our cohort of Norwegian participants receiving home care. Not all elderly people have the eHealth literacy to fully benefit from digital health services. Participants in cluster 4 (n=16) had the lowest scores in the eHealth Literacy Questionnaire scales in the READHY instrument and should be offered nondigital services or would need extensive management support. The demographic differences between the 4 clusters may inform stakeholders about which older people need the most training and support to take advantage of digital health care services.

Sverre Bergh, Jūratė Šaltytė Benth, Lisbeth Dyrendal Høgset, Britt Rydjord, Lars Kayser

Abstract:
Introduction: The presence of psychosis in Alzheimer’s disease (AD) is suggested to be associated with distinct molecular and neuropathological profiles in the brain.

Methods: We assessed brain DNA methylation in AD donors with psychosis (AD+P) and without psychosis (AD-P) using the EPIC array. Weighted gene correlation network analysis identified modules of co-methylated genes in a discovery cohort (PITT-ADRC: N = 113 AD+P, N = 40 AD-P), with validation in an independent cohort (BDR: N = 79 AD+P, N = 117 AD-P), with Gene Ontology and cell-type enrichment analysis. Genetic data were integrated to identify methylation quantitative trait loci (mQTLs), which were co-localized with GWAS for related traits.

Results: We replicated one AD+P associated module, which was enriched for synaptic pathways and in excitatory and inhibitory neurons. mQTLs in this module co-localized with variants associated with schizophrenia and educational attainment.

Discussion: This represents the largest epigenetic study of AD+P to date, identifying pleiotropic relationships between AD+P and related traits.

Highlights: DNA methylation was assessed in the prefrontal cortex in subjects with AD+P and AD-P. WGCNA identified six modules of co-methylated loci associated with AD+P in a discovery cohort. One of the modules was replicated in an independent cohort. This module was enriched for synaptic genes and in excitatory and inhibitory neurons. mQTLs mapping to genes in the module co-localized with GWAS loci for schizophrenia and educational attainment.

Morteza Kouhsar, Luke Weymouth, Adam R Smith, Jennifer Imm, Claudia Bredemeyer, Yehani Wedatilake, Ali Torkamani, Sverre Bergh, Geir Selbæk, Jonathan Mill, Clive Ballard, Robert A Sweet, Julia Kofler, Byron Creese, Ehsan Pishva, Katie Lunnon

Abstract

Late-life depression (LLD) has been linked to increased likelihood of dementia, although mechanisms responsible for this association remain largely unknown. One feature frequently observed in both LLD and dementia is elevated levels of plasma inflammatory markers. The present study aimed to compare the levels of 12 plasma inflammatory markers between older people with LLD and controls, and to explore whether these markers, along with clinical characteristics, can predict dementia in patients with LLD within 3 years of follow-up. Using multiple linear regression with stepwise adjustment, we compared levels of plasma inflammatory markers (IL-1β, IL-1ra, IL-6, IL-10, IL-17a, IL-18, IL-33, TNFα, CD40L, IFN-γ, CCL-2 and CCL-4) between 136 inpatients with LLD (PRODE cohort) and 103 cognitively healthy non-depressed controls (COGNORM cohort). In the PRODE cohort, follow-up data was available for 139 patients (of them 123 had data on baseline plasma inflammatory markers); 36 (25.9%) developed dementia by Year 3 (n = 31 for those with cytokine data). Using Cox proportional hazards regression, we explored whether inflammatory markers and clinical characteristics of LLD (age of onset, treatment response, number of episodes) predicted progression to dementia during follow-up. Levels of IL-1ra, CCL-2, CCL-4, IFN-γ and IL-17a were significantly higher in LLD patients compared to controls in the majority of models. However, none of the inflammatory markers predicted progression from LLD to dementia in the PRODE cohort. Among clinical features, only poor response to treatment significantly predicted higher risk of progression to dementia.

M Bocharova, T Borza, L O Watne, K Engedal, J T O’Brien, G Selbæk, A V Idland, J Hodsoll, A H Young & D Aarsland

Abstract
Background:
There is a growing concern and debate over the inappropriate use of analgesics and psychotropic medications by older adults, especially those with dementia. The long-term effects of the COVID-19 pandemic and lockdown measures on these prescriptions remain uncertain.

Aim:
The primary aim was to examine changes in the prescription of analgesics (opioids and other analgesics) and psychotropics (anxiolytics/sedatives, antidepressants, and antipsychotics) in Norwegian home-dwelling older adults before, during, and up to 2 years after the COVID-19 lockdown, with a particular focus on dementia status. Secondarily, we explored individual characteristics associated with changes in medication prescriptions.

Methods:
A prospective cohort study using baseline data from 10,464 participants (54% females, mean age 76 years [SD 5.8]) from the Norwegian Trøndelag Health Study (HUNT4 70+) linked with the Norwegian Prescription Database. Age- and education-adjusted Poisson regression was applied to examine changes in prescription fills, and multilevel mixed-effects linear regression was used to estimate the mean sum of defined daily dose (DDD) per person per period during the lockdown (March–September 2020) compared to that during the corresponding months (March–September) in 2019, 2021, and 2022.

Results:
Overall, prescriptions of opioids, other analgesics, and anxiolytics/sedatives were higher in 2022 than during the lockdown. People without dementia had increased prescriptions of opioids, other analgesics, and antidepressants after lockdown, whereas no changes were observed among those with dementia. Increases in prescriptions of opioids, other analgesics, anxiolytics/sedatives, and antidepressants between the lockdown and 2022 occurred mainly among those aged < 80 years, without comorbidities or mental distress, with good physical function, low fear of COVID-19, and no social isolation during COVID-19.

Conclusion:
An increase in analgesics and psychotropics after the lockdown was predominantly observed among younger-old and healthier participants. This indicates that in high-income countries, such as Norway, home-dwelling vulnerable individuals seem to have received adequate care. However, the pandemic may have increased the number of vulnerable individuals. These findings should be considered when identifying future nationwide stressors that may impair social interactions and threaten mental health. They also highlight the need to evaluate medication prescriptions for older adults after the pandemic.

Tanja Louise Ibsen, Ekaterina Zotcheva, Sverre Bergh, Debby Gerritsen, Gill Livingston, Hilde Lurås, Svenn-Erik Mamelund, Anne Marie Mork Rokstad, Bjørn Heine Strand, Richard C. Oude Voshaar & Geir Selbæk

Abstract

Background:
Childlessness, as well as having a high number of children, has been reported to be associated with an elevated risk of dementia compared to having 2–3 children. The mechanisms underlying these relationships are not well understood and may be mediated by different midlife risk factors. We examined the mediating role of various factors on the relationship between the number of children and dementia risk. These factors include socioeconomic factors (e.g., occupational complexity), psychosocial (e.g.., social activities, loneliness, life satisfaction), lifestyle (e.g., smoking, physical inactivity, alcohol intake), and chronic diseases (e.g., obesity, diabetes, depression, hearing impairment and hypertension).

Methods:
Using a historic cohort design, we included 9,745 participants born between 1931–48, with a mean age of 78.2 (SD = 6.4) years at the time of cognitive testing in the HUNT4 70 + sub-study (2017–2019). Further measures were obtained through data linkage between information from Statistics Norway and the HUNT1(1984–86), and HUNT2 (1995–97) Surveys. Causal mediation analyses using an inverse odd weighting approach were conducted to decompose the total effect of the number of children (0, 1, or 4 + children vs. 2–3) on the risk of dementia at age 70 + years into direct and indirect effects with mediators assessed at a mean age of 50.7 (SD = 6.4) years. The analyses were adjusted for age, sex, marital status at age 25 years, educational status, and religion assessed during HUNT3 (2006–2008).

Results:
Overall, 15.7% were diagnosed with dementia. The proportions with dementia by the number of children were 22.3% among those with no children, 21.4% for those with one child, 13% for those with 2–3 children (specifically, 12.6% for those with 2 children and 13.4% for those with 3 children), and 19.9% for those with 4 + children. Compared to the reference group of individuals with 2–3 children, the dementia risk was higher among the groups with no children (relative risk (RR): 1.30, 95% confidence interval (CI) (1.12, 1.51)), those with one child (RR: 1.30, 95% CI (1.14, 1.47)) and those with 4 + children (RR: 1.12, 95% CI (1.01, 1.24)). The elevated risks of dementia were not mediated by the socioeconomic, psychosocial, lifestyle, or chronic diseases related factors that we tested. Sex-stratified analysis showed higher dementia risk for men without children and women with one or 4 + children compared to those with 2–3 children, with similar patterns across sexes. None of the mediators contributed to mediation in either group. None of the mediators appeared to contribute through mediation in either group.

Conclusions:
Our findings suggest that the number of children—specifically being childless, having one child, or having four or more children—may influence the risk of dementia. These relationships were not mediated by psychosocial, lifestyle, and socioeconomic factors, or markers of chronic diseases in adulthood considered in this study.

Teferi Mekonnen, Vegard Skirbekk, Ekaterina Zotcheva, Bo Engdahl, Bernt Bratsberg, Astanand Jugessur, Catherine Bowen, Geir Selbæk, Hans-Peter Kohler, Jennifer R. Harris, Sarah E. Tom, Steinar Krokstad, Trine Holt Edwin, Yehani Wedatilake, Katrin Wolfova, Dana Kristjansson, Yaakov Stern, Asta Kristine Håberg & Bjørn Heine Strand