Forskningsartikler

Abstract:

Background: Delirium is common and age, frailty and dementia are risk-factors. The pathophysiology is complex and poorly understood, but age-related immune system changes may be key. This study aimed to measure markers of immune cell migration, accelerated immune ageing and blood-brain barrier permeability in community-dwelling, older people comparing those who developed ≥1 episode of delirium over 2 years with those that did not.

Methods: Baseline samples were collected from CASCADE participants who were followed up for 2 years. Delirium screening was performed weekly; positive screens or hospital admission triggered a delirium assessment. Serum was isolated, stored and analysed using a multiplex panel comparing levels between participants with and without delirium episodes.

Results: About 98 participants were included. Median age was 88 (IQR: 81.8-92.0), with 90.8% classified as frail. Forty-three participants (43.9%) experienced ≥1 delirium episodes. CCL2 (MCP-1) and CXCL2 (MIP-2α), measured in a stable state at baseline, were significantly higher in the delirium group compared to the no delirium group (13.38 (11.21-17.93) vs. 10.83 (9.03-14.64) P = .004) and (17.23 (11.80-24.22) vs. 13.49 (10.19-17.98) P = .031), respectively. When stratified by dementia status, the associations of CCL2 with delirium were maintained in both groups, but CXCL2 was only significantly higher in delirium in the subgroup without dementia.

Discussion: CCL2 and CXCL2 are chemokines involved in immune cell recruitment and markers of accelerated immune ageing. Future work should elucidate the role of immune cell recruitment and brain infiltration in delirium, to identify treatment targets. Furthermore, work should explore whether targeting immune ageing can reduce delirium risk.

Hannah Moorey, Hannah F Botfield, Maria Krogseth, Geir Selbaek, Daisy Wilson, Torgeir Bruun Wyller, Thomas Andrew Jackson

Abstract

Among the more than 90 identified genetic risk loci for late-onset Alzheimer’s disease (AD) and related dementias, the apolipoprotein E (APOE) gene ɛ2/ɛ3/ɛ4 polymorphisms remain the longstanding benchmark for genetic disease risk with a consistently large effect across studies1-10. Despite this massive signal, the exact mechanisms by which ɛ4 increases and ɛ2 decreases dementia risk remain poorly understood. Notably, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in ε4 carriers11-13, hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. HP1BP3, SLC50A1, PTPRC, NPAS3, DDHD1, CHST9, SMYD2, PRAMEF1 and GFRA1 emerged as new genomic signals for AD risk, appearing only when stratified by APOE carrier status. DDHD1 appeared especially promising, showing protective effects in ε4 carriers, being identified as an expression quantitative trait locus and being involved in rare neuronal diseases. Such APOE-stratified insights may help understand and overcome side effects, inform clinical trial enrollment strategies, and create the scientific basis for targeted, mechanism-driven therapies in neurodegenerative diseases.

Jesper Qvist Thomassen, Hampton Leonard, Brittany Ulms, Benjamin Grenier-Boley, Sami Heikkinen, Pablo Garcia-González, Atahualapa Castillo-Morales, Masataka Kikuchi, Jungsoo Gim, Han Cao, Fahri Küçükali, Najaf Amin, Dabin Yoon, Itziar de Rojas, Pilar Alvarez Jerez, Victoria Alvarez, Beatrice Arosio, Céline Bellenguez, Sverre Bergh, Kimberley Billingsley, Cornelis Blauwendraat, Merce Boada, Barbara Borroni, Paola Bossù, María J Bullido, Antonio Daniele, Ángel Carracedo, Alexandre de Mendonça, Mark Cookson, Jürgen Deckert, Martin Dichgans, Srdjan Djurovic, Oriol Dols-Icardo, Carole Dufouil, Emrah Düzel, Valentina Escott-Price, Tormod Fladby, Laura Fratiglioni, Amy K Y Fu, Daniela Galimberti, Jose Maria García-Alberca, Vilmantas Giedraitis, Guillermo Garcia-Ribas, Caroline Graff, Timo Grimmer, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Jakub Hort, Frank Jessen, Kendall Jensen, Caroline Jonson, Yoontae Kim, Nicole Kuznetsov, Ville Leinonen Anssi Lipponen, Jiao Luo, Mary Makarious, Henna Martiskainen, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Pablo Mir, Akinori Miyashita, Susanne Moebus, Kin Y Mok, Laura Molina Porcel, Fermin Moreno, Benedetta Nacmias, Lucilla Parnetti, Pau Pastor, Jordi Pérez-Tur, Oliver Peters, Yolande A L Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Innocenzo Rainero, Luis M Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Arvid Rongve, Giacomina Rossi, Jose Luis Royo, Dan Rujescu, Ingvild Saltvedt, María Eugenia Sáez, Raquel Sánchez-Valle, Florentino Sanchez-Garcia, Nicolai Sandau, Nikolaos Scarmeas, Katja Scheffler, Norbert Scherbaum, Anja Schneider, Geir Selbæk, Davide Seripa, Vincenzo Solfrizzi, Marco Spallazzi, Alessio Squassina, Eystein Stordal, Niccoló Tesi, Lucio Tremolizzo, Kumar P Tripathi, Wiesje M van der Flier, Julie Williams, Jens Wiltfang, Dag Aarsland, Andrew B Singleton, Philippe Amouyel, Stéphanie Debette, Magda Tsolaki, Gael Nicolas, Sven van der Lee, Henne Holstege, Maria Victoria Fernandez, Patrick Gavin Kehoe, Kristel Sleegers, Martin Ingelsson, Roberta Ghidoni, Ole A Andreassen, Peter A Holmans, Pascual Sánchez-Juan, Rebecca Sims, Nancy Y Ip, Kun Ho Lee, Takeshi Ikeuchi, Alfredo Ramirez, Agustin Ruiz, Mikko Hiltunen, Jean-Charles Lambert, Cornelia van Duijn, Mike Nalls, Ruth Frikke-Schmidt

Abstract

Background: This longitudinal cohort study aimed to determine whether mental health problems in midlife are linked to frailty after age 70, as measured using two sets of frailty criteria.

Methods: We used data from 27,958 adults aged 35-60 years in the Trøndelag Health Study (HUNT1, 1984-1986), with frailty outcomes assessed in 9,956 participants aged 70 years and older (HUNT4, 2017-2019). Mental health at baseline was self-reported. Frailty at follow-up was measured using both the Fried criteria and the 35-item HUNT4-Frailty Index. Linear regression models estimated frailty differences by baseline mental health status, adjusted for sociodemographic and lifestyle factors, stratified by age. We applied inverse probability weighting and multiple imputation to reduce selection bias.

Results: Mental health problems at age 35-49 at baseline were associated with 0.52 (95% CI: 0.35-0.69) higher Fried scores and 0.066 (95% CI: 0.048-0.084) higher HUNT4-FI scores at follow-up. For ages 50-60, Fried scores and HUNT4-FI scores were higher by 0.30 (95% CI: -0.02-0.63) and 0.037 (95% CI: 0.006-0.068), respectively.

Conclusion: We observed that midlife mental health problems were associated with higher frailty levels three decades later, across two commonly used frailty models. These findings underscore the importance of both psychological and physical factors in ageing.

Ingebjørg L Kyrdalen, Geir Selbæk, Emiel O Hoogendijk, Ellen Melbye Langballe, Heidi Ormstad, Håvard Kjesbu Skjellegrind, Bjørn Heine Strand, Karen Sverdrup, Pernille Thingstad, Gro Gujord Tangen

Abstract

Background: Pain is common among people living with dementia (PLWD) in the community and is associated with substantial negative consequences for both individuals and caregivers; however, knowledge regarding its prevalence and assessment in a community living population with dementia remains limited. The aim of this systematic review was to examine the prevalence of pain and the pain assessment inventories used among PLWD at home.

Method: This systematic review was registered in PROSPERO (CRD420251136436) and was conducted in accordance with the PRISMA 2020 statement. The searched databases include PubMed, MEDLINE, CINAHL, APA PsycInfo, AgeLine, the Cochrane Library, and Idunn, covering articles published from January 2000 to February 2026. Quantitative observational studies that reported pain through self-report questionnaires, staff- and/or caregiver- assessments were included to define the prevalence of pain in samples or subsamples of PLWD at home. The database search identified 1,296 records, of which 25 articles from 22 studies were included in the final review.

Results: Sample sizes ranged from 36 to 1,379 PLWD at home. Pain was reported as any pain occurring within a defined timeframe, pain present on the day of assessment, pain meeting predefined severity criteria, or pain interfering with daily activities. The prevalence of pain among PLWD at home was consistently high, with higher prevalence estimates reported in studies assessing any pain compared with those applying severity or consequence-based criteria. The prevalence of any pain during the past month was found to vary between 36 and 76%. Considerable methodological heterogeneity was observed in terms of pain definitions, assessment methods, and inclusion criteria, which makes comparisons across studies difficult.
Conclusion: The overall high prevalence of pain identified in this review underscores the need for systematic and standardized pain assessment for PLWD at home.

Anne-S. Helvik, Büşra Nur Temür, Sverre Bergh and Kjerstin Tevik

Abstract

Dementia care across Europe is characterized by substantial regional disparities in research participation, funding, and care practices, which challenge the development of equitable and inclusive research agendas. The PANEUCARE consortium adopted a pan-European, co-produced approach that integrates professional expertise with the perspectives of people living with dementia and caregivers to identify priorities for a more equitable dementia research landscape. Insights were generated through two workshops with dementia professionals and consultation groups involving people living with dementia and caregivers, followed by deliberative synthesis to explore common challenges, regional barriers, and shared research priorities. Participants highlighted persistent issues including workforce shortages, delayed diagnosis, fragmented care pathways, caregiver burden, and the underrepresentation of Southern and Eastern European contexts in research. At the same time, examples of local innovation, such as community-based services, cross-sector collaboration, and the use of digital tools, demonstrated context-specific resilience and opportunities for cross-regional learning. Priority areas for future research included strengthening cross-regional collaboration, addressing workforce development, improving culturally sensitive and post-diagnostic care, enhancing support for caregivers, and promoting more inclusive participation in research. These insights informed the development of the EQUITABLE framework (Equity, Quality, Urgency, Involvement, Transdisciplinary collaboration, Adaptability, Budget-consciousness, Linguistic and cultural sensitivity, and Engagement), which provides actionable guidance for designing inclusive and context-sensitive dementia research across Europe. By bringing together professional expertise and lived experience, PANEUCARE highlights how Europe’s diversity in dementia care can be leveraged as a resource for shared learning and policy development, supporting a more equitable, sustainable, and responsive European dementia research landscape.

Maria Isabel Cardona, Clarissa Giebel, Anthony Scerri, Anthea Innes, Ninoslav Mimica, Osman Kučuk, T. Rune Nielsen, Jūratė Macijauskienė, Carolien Smits, Carmel Geoghegan, Soraya Moradi-Bachiller, Anne Marie Rokstad, Iva Holmerova, Elżbieta Trypka, Ágnes Egervári, Raluca Sfetcu, Marija Taneska, Péter Hegedűs, Iryna Shevchenko, Svetlana Iloski, Thanos Chatzikostopoulos, Jochen René Thyrian

Abstract

Purpose: To describe intrinsic capacity (IC) distribution across age and sex and investigate its subdomains’ association with self-perceived health in home-dwelling older adults.

Methods: This cross-sectional study used population-based data from the Trøndelag Health Study (HUNT). Self-perceived health was assessed by a 4-point Likert scale and dichotomized into good or poor health. IC consists of five subdomains (vitality, locomotion, cognition, psychological, and sensory capacity), assessed in line with the WHO recommendations. Capacity in locomotion and cognition was assessed by the SPPB and MoCA, while the remaining subdomains were assessed through questionnaires. Associations between subdomains and self-perceived health were examined using simple and multiple regression models, adjusting for age and education.

Results: We included 8718 home-dwelling older adults (aged 70-101 years; 52.5% women). Good health was reported by 69.8% among those < 85 years and by 48.6% among those ≥ 85 years. High capacity in ≥ 3 subdomains was observed in 79.3% and 40.9% among individuals < 85 years and ≥ 85 years, respectively. High locomotor capacity showed the strongest association with good self-perceived health. The probability of poor self-perceived health increased with lower IC, but among women, significantly less by older age and more by higher education.

Conclusion: We observed a strong association between IC and self-perceived health, suggesting that IC is closely linked to individuals’ self-perceived health. Our findings support IC as a relevant tool in the shift toward preventive, health-promoting care, and we believe the use of IC can help tailor interventions to optimize functional ability and well-being.

Kjerstin Næss Melsæter, Turid Follestad, Gro Gujord Tangen, Beatrix Vereijken, Pernille Thingstad

Abstract:
Background: New knowledge about the process leading to crises among community-dwelling frail patients, such as acute hospital admissions, may contribute to improved understanding, prevention, and new approaches to future crises. The aim of this study was to explore the development of crises among frail patients as documented in the patient records by home care services and general practitioners.

Methods: This study comprised a qualitative process analysis of documents from electronic patient records systems retrieved from home care services and general practitioners in ten municipalities in Norway for 20 patients.

Findings: The analysis showed that the structure of the examined patient records influences the ability to disclose the processes leading to crises. Events within the crisis process were often described without addressing the underlying reasons for their occurrence. Furthermore, the development of a crisis was found to follow individual and complex pathways for each patient.

Janne Myhre, Sverre Bergh, Ingvild Hjorth Feiring, Lisbeth Dyrendal Høgset Lisbeth, Øyvind Kirkevold og Bjørn Lichtwarck

Abstract: 

Background: Idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD) are neurodegenerative disorders with partly overlapping clinical features. Since the treatment is different, we need better knowledge about how the cognitive profile differs between these conditions.

Objective: We aimed to compare the cognitive profile of iNPH patients with that of a large cohort of confirmed AD patients.

Methods: Patients diagnosed with iNPH and accepted for shunt surgery were compared with patients with biomarker verified Alzheimer’s disease in The Norwegian Register of Persons Assessed for Cognitive symptoms (NorCog). All patients underwent a standardized cognitive assessment with age and education adjusted z-scores. We used the Clinical Dementia Rating Scale (CDR) to adjust for disease severity. Since the cognitive score distributions were highly skewed, we used nonparametric analyses stratified by CDR stage combined with multinomial logistic regression.

Results: In total, 276 iNPH patients were compared to 1113 AD patients. iNPH patients performed significantly poorer on phonemic fluency [median z-score difference (AD-iNPH) 0.30, 95% confidence interval (CI) 0.20 to 0.50], but significantly better on other cognitive tests, in particular immediate (median difference -0.35, 95% CI -0.49 to -0.20) and delayed recall (median difference -0.46, 95% CI -0.59 to -0.34). The differences persisted after adjustment for CDR and were most pronounced in early stages of the disease.

Conclusions: iNPH seems to affect phonemic fluency more and memory less than AD. As the disease progresses, the cognitive profiles become more similar, and the conditions cannot be distinguished by cognitive tests.

Magnhild S Dejgaard, Per Kristian Eide, Gro Gujord Tangen, Eva Skovlund, Geir Selbæk, Torgeir Bruun Wyller

Abstract

Introduction: Most people with dementia in Norway live at home, and maintaining physical, social and spiritual activity remains a basic need. Yet research has focused on women as caregivers rather than women living with dementia. Consequently, more knowledge is needed into what women receiving home care service consider important in daily life to tailor health care services and to understand how these women experience participating in activities.

Objective: The aim of this study was to describe what women with dementia who receive home care service consider important in their daily lives.

Methods: This study employed an exploratory-descriptive design. Data were collected using individual semi-structured interviews with eight older women with dementia with mild to moderate cognitive impairment who received home care service. Data were analysed using manifest qualitative content analysis.

Results: The data analysis identified three categories: The need to be physically active and spend time outdoors, The need to staying socially connected and The need for meaningful activities.

Conclusion: This study provides insight into what women with dementia who receive home care service consider important in their daily lives. The need for meaning in daily life can be met in different ways, and it is important to tailor activities for women with dementia.

Simen A Steindal, Ingebjørg Haugen, Orla Brady, Knut Engedal, Benedicte Sørensen Strøm