Forskningsartikler

Abstract:

Introduction: Functional ability is vital for independent living. In this study, we explored functional trajectories of instrumental activities of daily living (IADL) and participation in working- or leisure activities (role function) in older adults undergoing radiotherapy (RT) and aimed to identify individuals at risk of functional decline.

Materials and methods: Patients were ≥ 65 years and received RT with curative or palliative intent. IADL was assessed by Nottingham Extended Activities of Daily Living (NEADL) scale at start and end of RT, and at 2, 8, and 16 weeks after treatment. Simultaneously, patients reported role function and symptoms using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (QLQ-C30). Data were analysed by growth mixture modelling and linear mixed models.

Results: We included 258 patients, mean age 73.5 years, 129 (50%) were female, and 232 (89.9%) had an Eastern Cooperative Oncology Group performances status scale (PS) of 0-1. For both NEADL and the role function scale of the QLQ-C30, four groups with distinct trajectories were identified. The group with the poorest baseline scores showed a clinically significant decline. Patients in this group were older, had more geriatric impairments, poorer PS and received palliative RT. Fatigue, pain and loss of appetite were associated with poorer NEADL and role function scores during and after RT.

Discussion: Although most patients preserved their IADL and role function during RT treatment, patients with poor IADL and role function at the start of RT were at risk of further functional decline. This knowledge should be incorporated into treatment decision-makings. Geriatric impairments and symptom burden are important targets for supportive measures and should be identified and assessed both before and during treatment.

Heidi Marie Tjugum, Siri Rostoft, Jūratė Šaltytė Benth, May Ingvild Volungholen Sollid, Guro Falk Eriksen, Tom Borza, Bjørn Henning Grønberg, Sverre Bergh, Øyvind Kirkevold, Ola Berger Christiansen, Line Merethe Oldervoll, Asta Bye, Marit Slaaen

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