Forskningsartikler

Bakgrunn
Antallet personer med demens forventes tredoblet innen 2050. Vi presenterer forekomsttall for demens og mild kognitiv svikt i Trondheim og viser hvordan vekting for frafall og bostatus påvirker forekomsttallene når vi sammenligner Trondheim med Nord-Trøndelag.
Materiale og metode
Personer i alderen 70 år og eldre i Trondheim ble invitert til å delta i helseundersøkelsen HUNT4 (den fjerde Helseundersøkelsen i Trøndelag) Trondheim 70+. Deltakerne ble intervjuet og gjennomgikk kognitiv testing. Et diagnoseteam satte diagnosene demens og mild kognitiv svikt. Frafallsvekter som justerte for utvalgsskjevheter, ble benyttet i sammenligningen av Trondheim og Nord-Trøndelag.
Resultater
Demensforekomsten i Trondheim ble estimert til 16,2 % for aldersgruppen 70 år og eldre etter vekting for skjevt frafall med henblikk på alder, kjønn, utdanning og andel sykehjemsbeboere. Ujustert demensforekomst var 21,0 % i Trondheim og 15,7 % i Nord-Trøndelag. Etter vekting ble forekomsten tilnærmet identisk i de to utvalgene.
Fortolkning
Å vekte for skjevt frafall har stor betydning for å få representative tall i forekomstundersøkelser av demens.
Hovedfunn
Forekomsten av demens og mild kognitiv svikt hos personer i alderen 70 år og eldre i Trondheim ble estimert til henholdsvis 16,2 % og 35,6 %.
Ujustert demensforekomst var 21,0 % for Trondheim og 15,7 % for Nord-Trøndelag, men etter vekting for skjevt frafall med hensyn til alder, kjønn, utdanning og sykehjem ble forekomsten tilnærmet identisk i de to utvalgene.

Linda Gjøra, Bjørn Heine Strand, Knut Engedal, Linda Ernstsen, Christian Myrstad, Håvard Skjellegrind, Pernille Thingstad, Geir Selbæk

Abstract

Physical activity (PA) might influence the risk or progression of chronic pain through pain tolerance. Hence, we aimed to assess whether habitual leisure-time PA level and PA change affects pain tolerance longitudinally in the population. Our sample (n = 10,732; 51% women) was gathered from the sixth (Tromsø6, 2007-08) and seventh (Tromsø7, 2015-16) waves of the prospective population-based Tromsø Study, Norway. Level of leisure-time PA (sedentary, light, moderate, or vigorous) was derived from questionnaires; experimental pain tolerance was measured by the cold-pressor test (CPT). We used ordinary, and multiple-adjusted mixed, Tobit regression to assess 1) the effect of longitudinal PA change on CPT tolerance at follow-up, and 2) whether a change in pain tolerance over time varied with level of LTPA. We found that participants with high consistent PA levels over the two surveys (Tromsø6 and Tromsø7) had significantly higher tolerance than those staying sedentary (20.4 s. (95% CI: 13.7, 27.1)). Repeated measurements show that light (6.7 s. (CI 3.4, 10.0)), moderate (CI 14.1 s. (9.9, 18.3)), and vigorous (16.3 s. (CI 6.0, 26.5)) PA groups had higher pain tolerance than sedentary, with non-significant interaction showed slightly falling effects of PA over time. In conclusion, being physically active at either of two time points measured 7-8 years apart was associated with higher pain tolerance compared to being sedentary at both time-points. Pain tolerance increased with higher total activity levels, and more for those who increased their activity level during follow-up. This indicates that not only total PA amount matters but also the direction of change. PA did not significantly moderate pain tolerance change over time, though estimates suggested a slightly falling effect possibly due to ageing. These results support increased PA levels as a possible non-pharmacological pathway towards reducing or preventing chronic pain.

Anders Pedersen Årnes, Christopher Sievert Nielsen, Audun Stubhaug, Mats Kirkeby Fjeld, Aslak Johansen, Bente Morseth, Bjørn Heine Strand, Tom Wilsgaard, Ólöf Anna Steingrímsdóttir

Background: Observational tools can support the understanding of the complex needs of older people with dementia and aid delivery of person-centred care. However, existing tools are complex and resource intensive to use.

Objectives: To develop and evaluate the acceptability and feasibility of a low-resource, observational tool to support staff reflection and practice development.

Methods: Intervention development of the Person-Centred Observation and Reflection Tool (PORT) and acceptability and feasibility study, using surveys and focus groups in the UK, Norway and Spain.

Results: PORT was reported as easy, accessible and acceptable to use. The observation was identified as powerful for individual staff development and provided an evidence-based source for underpinning individualised care planning. Potential time challenges associated with implementation were identified.

Conclusion: Initial evaluation indicates PORT is an acceptable and feasible tool for use in health and social care settings for older people. Further research is needed on implementation models and the impacts of PORT use.

Implications for practice: PORT may be a useful tool to support individual staff development in care settings and person-centred care planning for people with dementia.

Claire Surr, Anne Marie Mork Rokstad, Josep Vila Miravent, Elena Fernandez, Aukje Post, Carol Fusek, Dawn Brooker

Genotypes causing pregnancy loss and perinatalmortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations.
In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.

Asmundur Oddsson… Geir Selbæk…Daniel F. Gudbjartsson

Background: Neuroinflammation is involved in the pathophysiology of Alzheimer’s disease (AD), including immune-linked genetic variants and molecular pathways, microglia and astrocytes. Multiple Sclerosis (MS) is a chronic, immune-mediated disease with genetic and environmental risk factors and neuropathological features. There are clinical and pathobiological similarities between AD and MS. Here, we investigated shared genetic susceptibility between AD and MS to identify putative pathological mechanisms shared between neurodegeneration and the immune system.

Methods: We analysed GWAS data for late-onset AD (N cases = 64,549, N controls = 634,442) and MS (N cases = 14,802, N controls = 26,703). Gaussian causal mixture modelling (MiXeR) was applied to characterise the genetic architecture and overlap between AD and MS. Local genetic correlation was investigated with Local Analysis of [co]Variant Association (LAVA). The conjunctional false discovery rate (conjFDR) framework was used to identify the specific shared genetic loci, for which functional annotation was conducted with FUMA and Open Targets.

Results: MiXeR analysis showed comparable polygenicities for AD and MS (approximately 1800 trait-influencing variants) and genetic overlap with 20% of shared trait-influencing variants despite negligible genetic correlation (rg = 0.03), suggesting mixed directions of genetic effects across shared variants. conjFDR analysis identified 16 shared genetic loci, with 8 having concordant direction of effects in AD and MS. Annotated genes in shared loci were enriched in molecular signalling pathways involved in inflammation and the structural organisation of neurons.

Conclusions: Despite low global genetic correlation, the current results provide evidence for polygenic overlap between AD and MS. The shared loci between AD and MS were enriched in pathways involved in inflammation and neurodegeneration, highlighting new opportunities for future investigation.

Vera Fominykh, Alexey A Shadrin, Piotr P Jaholkowski, Shahram Bahrami, Lavinia Athanasiu, Douglas P Wightman, Emil Uffelmann, Danielle Posthuma, Geir Selbæk, Anders M Dale, Srdjan Djurovic, Oleksandr Frei, Ole A Andreassen

Late-life depression (LLD) has been linked to increased likelihood of subsequent 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. PRODE (Prognosis of Depression in the Elderly) is a prospective naturalistic study of patients with LLD (N=152; aged 60+). Patients were followed up for 3 years; follow-up data was available for 138 patients, and 36 (26.1%) developed dementia by year 3. Plasma inflammatory markers data were available for 136 patients at baseline for the following range of cytokines and chemokines: IL-1β, IL-1ra, IL-6, IL-10, IL-17a, IL-18, IL-33, TNFα, CD40L, IFN-γ, CCL-2 and CCL-4. Levels of plasma inflammatory markers were compared between 136 LLD patients and healthy controls (n=103), using first multiple linear regression (inflammatory markers as outcome) with stepwise adjustment, and then binary logistic regression with depression status (LLD vs controls) as outcome. Further, we explored whether inflammatory markers and clinical characteristics of LLD (age of onset, course) predicted progression from LLD to dementia using Cox regression. Levels of IL-1ra, IFN-γ, CCL-2, CCL-4 and IL-17a were significantly higher in LLD patients compared to controls. However, none of the inflammatory markers predicted progression from LLD to dementia. Among clinical features, only poor response to treatment significantly predicted higher risk of progression to dementia. In summary, this study replicated previous findings of an increase in inflammatory markers in LLD but did not find evidence they had increased risk of developing future dementia.

Dag Aarsland, Allan Young, Knut Engedal, John O’Brien, Geir Selbaek, Ane-Victoria Idland, Leiv-Otto Watne, Tom Borza, Mariia Bocharova

Background: Studies exploring the possible protective effect of coffee and tea consumption on dementia have shown inconsistent results so far. We aimed to investigate whether consumption of tea and different types of coffee at midlife are associated with dementia later in life and whether sex or ApoE4 influence such association.
Methods: We included 7381 participants from the Norwegian HUNT Study. Self-reported questionnaires assessed daily consumption of coffee and tea at baseline. After 22 years, individuals 70 years or older were screened for cognitive impairment.
Results: General coffee consumption and tea consumption was not associated with dementia risk. Compared to daily consumption of 0–1 cups of coffee, daily consumption of ≥8 cups of boiled coffee was associated with increased dementia risk in women (OR: 1.83, 95% CI: 1.10–3.04, p-value for trend = 0.03) and daily consumption of 4–5 cups of other types of coffee was associated with a decrease in dementia risk in men (OR: 0.48, 95% CI: 0.32–0.72, p-value for trend = 0.05). Furthermore, the association between boiled coffee and increased dementia risk was only found in ApoE4 non-carriers. Differences by sex or ApoE4 carrier status were not supported by strong statistical evidence for interaction. Tea consumption was not associated with dementia risk.
Conclusion: type of coffee may play a role in the direction of the association between coffee-drinking habits and dementia later in life.

Denise Abbel, Bjørn Olav Åsvold, Marit Kolberg, Geir Selbæk, Raymond Noordam and Håvard Kjesbu Skjellegrind

Background: The declining incidence of stroke, ischemic heart disease (IHD) and dementia (the triple threat) in Norway encourages further investigation. We analysed the risks and trends of the three conditions using data from the Global Burden of Disease study (GBD).

Methods: We used GBD 2019 estimations for age-, sex-, and risk factor-specific incidence and prevalence of “the triple threat” and their risk factor-attributed deaths and disability combined and their age-standardised rates per 100,000 population in 2019 and their changes during 1990-2019. Data are presented in means and 95% uncertainty intervals (UI).

Results: In 2019, 71.1 thousand Norwegian were living with dementia, 157.2 thousand with IHD, and 95.2 thousand with strokes. In 2019, there were 9.9 thousand (8.5 to 11.3) new cases of dementia (35.0% increase since 1990), 17.0 thousand (14.6 to 19.6) with IHD (3.6% decrease), and 8.0 thousand (7.0 to 9.1) with strokes (12.9% decrease) in Norway. During 1990-2019, their age-standardised incidence rates decreased significantly; dementia by -5.4% (-8.4 to -3.2), IHD by -30.0% (-31.4 to -28.6), and stroke by -35.3% (-38.3 to -32.2), respectively. There were significant declines in the attributable risks to both ENVIRONMENTAL and behavioural factors in Norway, but contradictory trends for metabolic risk factors during 1990-2019.

Conclusions: The risk of “the triple threat” conditions is declining in Norway, despite the increased prevalence. This offers the opportunity to find out why and how and to accelerate their joint prevention through new approaches and the promotion of the National Brain Health Strategy.

Abolfazl Avan, Anne Hege Aamodt, Geir Selbaek, Gunnar Bovim, Claudio L A Bassetti, Paul Boon, Wolfgang Grisold, Vladimir Hachinski

Sammendrag

Hensikt: Studien belyser hvilke erfaringer fysioterapeuter har med å gi fysioterapibehandling til beboere med langtidsopphold i norske sykehjem, og hvordan fysioterapeutene er involvert i behandlingen av beboere i livets sluttfase.

Design, materiale og metode: Artikkelen er basert på eksplorerende kvalitative intervjuer med seks fysioterapeuter som jobber i sykehjem. Intervjuene var semistrukturerte og datamaterialet ble analysert med systematisk tekstkondensering.

Funn: Deltakerne inntar i stor grad en tradisjonell fysioterapeutrolle med fokus på trening. De anerkjenner at fysioterapeuter har kunnskap og ferdigheter som er relevante for beboerne i livets sluttfase, men er i liten grad involvert i det tverrfaglige teamet rundt den døende.

Konklusjon: Fysioterapeutene som jobber i langtidsavdelinger i sykehjem bruker mesteparten av arbeidstiden sin på tradisjonell fysioterapi. De er ikke er involvert i lindrende behandling og omsorg i livets sluttfase, men mener at de har relevant kunnskap – og således er en ubrukt ressurs. Mangelen på fysioterapeuter i det tverrfaglige palliative teamet er et resultat av at fysioterapeutene selv ikke gir uttrykk for at de ønsker å bidra, samtidig som leger og sykepleiere ikke etterspør deres kunnskap på dette området. Organiseringen av fysioterapitjenesten i sykehjem ser også ut til å kunne påvirke det tverrfaglige samarbeidet.

Kristine Bjorheim Bøe, Tone Dahl-Michelsen & Elisabeth Wiken Telenius