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

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

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

Introduction: There is a pressing need for non-invasive, cost-effective tools for early detection of Alzheimer’s disease (AD).

Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Cox proportional models were conducted to develop a multimodal hazard score (MHS) combining age, a polygenic hazard score (PHS), brain atrophy, and memory to predict conversion from mild cognitive impairment (MCI) to dementia. Power calculations estimated required clinical trial sample sizes after hypothetical enrichment using the MHS. Cox regression determined predicted age of onset for AD pathology from the PHS.

Results: The MHS predicted conversion from MCI to dementia (hazard ratio for 80th versus 20th percentile: 27.03). Models suggest that application of the MHS could reduce clinical trial sample sizes by 67%. The PHS alone predicted age of onset of amyloid and tau.

Discussion: The MHS may improve early detection of AD for use in memory clinics or for clinical trial enrichment.

Highlights: A multimodal hazard score (MHS) combined age, genetics, brain atrophy, and memory. The MHS predicted time to conversion from mild cognitive impairment to dementia. MHS reduced hypothetical Alzheimer’s disease (AD) clinical trial sample sizes by 67%. A polygenic hazard score predicted age of onset of AD neuropathology.

Emilie T Reas, Alexey Shadrin, Oleksandr Frei, Ehsan Motazedi, Linda McEvoy, Shahram Bahrami, Dennis van der Meer, Carolina Makowski, Robert Loughnan, Xin Wang, Iris Broce, Sarah J Banks, Vera Fominykh, Weiqiu Cheng, Dominic Holland, Olav B Smeland, Tyler Seibert, Geir Selbaek, James B Brewer, Chun C Fan, Ole A Andreassen, Anders M Dale; Alzheimer’s Disease Neuroimaging Initiative

Purpose: To synthesize qualitative empirical research that expands the knowledge of what people with dementia consider to be essential for daily living in a dementia-friendly society.

Methods: The authors searched phrases in the databases AgeLine, CINAHL, EMBASE, MedLine, PsycINFO, PubMed, ORIA, SveMed+, and Cochrane Library. Research articles that involved people with dementia and were conducted in Western countries, written in English, published in peer-reviewed academic journals using qualitative methods, and published within the past decade were included. The research included was critically and systematically appraised using the critical appraisal skills program checklist for qualitative research, and the findings were analyzed according to Graneheim and Lundman’s method of qualitative content analysis.

Results: Overall, 1122 records-561 from 2019 and 561 from 2021-were identified through the search, and nine studies were included in the final synthesis. The studies included were from the United Kingdom (five studies), Australia (three studies), and New Zealand (one study). Through the analysis process, the following main theme emerged: giving voice to people with dementia, which summarizes the essence of what people with dementia believe is essential for daily living in a dementia-friendly society. The main theme covered two themes: a sense of being valued and a sense of being safeguarded, each of which contained subthemes.

Conclusion: To meet the WHO’s and the governments worldwide intention to develop dementia-friendly societies, further research should focus on the voices of people with dementia. By including those concerned, the political goals of a dementia-friendly society can be achieved.

Johanne Alteren, Aud Johannessen, Anne Marit Lyberg, Inger-Lise Magnussen

Background: The Mini-Mental State Examination (MMSE), a simple test for measuring global cognitive function, is frequently used to evaluate cognition in older adults. To decide whether a score on the test indicates a significant deviation from the mean score, normative scores should be defined. Moreover, because the test may vary depending on its translation and cultural differences, normative scores should be established for national versions of the MMSE.

Objective: We aimed to examine normative scores for the third Norwegian version of the MMSE.

Methods: We used data from two sources: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) and the Trøndelag Health Study (HUNT). After persons with dementia, mild cognitive impairment, and disorders that may cause cognitive impairment were excluded, the sample contained 1,050 cognitively healthy persons, 860 from NorCog, and 190 from HUNT, whose data we subjected to regression analyses.

Results: The normative MMSE score varied from 25 to 29, depending on years of education and age. More years of education and younger age were associated with higher MMSE scores, and years of education was the strongest predictor.

Conclusion: Mean normative MMSE scores depend on test takers’ years of education and age, with level of education being the strongest predictor.

Knut Engedal, Jūratė Šaltytė Benth, Linda Gjøra, Håvard Kjesbu Skjellegrind, Marit Nåvik, Geir Selbæk

Background: Mobility impairments, in terms of gait and balance, are common in persons with dementia. To explore this relationship further, we examined the associations between mobility and cerebrospinal fluid (CSF) core biomarkers for Alzheimer’s disease (AD).
Methods: In this cross-sectional study, we included 64 participants [two with subjective cognitive decline (SCD), 13 with mild cognitive impairment (MCI) and 49 with dementia] from a memory clinic. Mobility was examined using gait speed, Mini-Balance Evaluation Systems test (Mini-BESTest), Timed Up and Go (TUG), and TUG dual-task cost (TUG DTC). The CSF biomarkers included were amyloid-β 42 (Aβ42), total-tau (t-tau), and phospho tau (p-tau181). Associations between mobility and biomarkers were analyzed through correlations and multiple linear regression analyses adjusted for (1) age, sex, and comorbidity, and (2) SCD/MCI vs. dementia.
Results: Aβ42 was significantly correlated with each of the mobility outcomes. In the adjusted multiple regression analyses, Aβ42 was significantly associated with Mini- BESTest and TUG in the fully adjusted model and with TUG DTC in step 1 of the adjusted model (adjusting for age, sex, and comorbidity). T-tau was only associated with TUG DTC in step 1 of the adjusted model. P-tau181 was not associated with any of the mobility outcomes in any of the analyses.
Conclusion: Better performance on mobility outcomes were associated with higher levels of CSF Aβ42. The association was strongest between Aβ42 and Mini-BESTest, suggesting that dynamic balance might be closely related with AD-specific pathology.

Gro Gujord Tangen, Karen Sverdrup, Kristin Taraldsen, Karin Persson, Knut Engedal, Peter Bekkhus-Wetterberg and Anne-Brita Knapskog