Forskningsartikler

Background
Geriatric assessment and management (GAM) improve outcomes in older patients with cancer treated with surgery or chemotherapy. It is unclear whether GAM may provide better function and quality of life (QoL), or be cost-effective, in a radiotherapy (RT) setting.

Methods
In this Norwegian cluster-randomised controlled pilot study, we assessed the impact of a GAM intervention involving specialist and primary health services. It was initiated in-hospital at the start of RT by assessing somatic and mental health, function, and social situation, followed by individually adapted management plans and systematic follow-up in the municipalities until 8 weeks after the end of RT, managed by municipal nurses as patients’ care coordinators. Thirty-two municipal/city districts were 1:1 randomised to intervention or conventional care. Patients with cancer ≥ 65 years, referred for RT, were enrolled irrespective of cancer type, treatment intent, and frailty status, and followed the allocation of their residential district. The primary outcome was physical function measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (QLQ-C30). Secondary outcomes were overall quality of life (QoL), physical performance, use and costs of health services. Analyses followed the intention-to-treat principle. Study registration at ClinicalTrials.gov ID NCT03881137.

Results
We included 178 patients, 89 in each group with comparable age (mean 74.1), sex (female 38.2%), and Edmonton Frail Scale scores (mean 3.4 [scale 0–17], scores 0–3 [fit] in 57%). More intervention patients received curative RT (76.4 vs 61.8%), had higher irradiation doses (mean 54.1 vs 45.5 Gy), and longer lasting RT (mean 4.4 vs 3.6 weeks). The primary outcome was completed by 91% (intervention) vs 88% (control) of patients. No significant differences between groups on predefined outcomes were observed. GAM costs represented 3% of health service costs for the intervention group during the study period.

Conclusions
In this heterogeneous cohort of older patients receiving RT, the majority was fit. We found no impact of the intervention on patient-centred outcomes or the cost of health services. Targeting a more homogeneous group of only pre-frail and frail patients is strongly recommended in future studies needed to clarify the role and organisation of GAM in RT settings.

Marit Slaaen, Inga Marie Røyset, Ingvild Saltvedt, Bjørn Henning Grønberg, Vidar Halsteinli, Øystein Døhl, Corinna Vossius, Øyvind Kirkevold, Sverre Bergh, Siri Rostoft, Line Oldervoll, Asta Bye, Line Melby, Tove Røsstad, Guro Falk Eriksen, May Ingvild Volungholen Sollid, Darryl Rolfson & Jūratė Šaltytė Benth

Background: Changes in alcohol consumption may affect older adults’ health. We examined prevalence and changes in the alcohol consumption of older women and men (≥65 years) in Norway over a 24-year period.

Methods: Data from three population-based health surveys (The Trøndelag Health Study-HUNT2 1995-97, HUNT3 2006-08, HUNT4 2017-19) were used. Alcohol consumption was measured using self-reported measures and an objective measure of alcohol consumption (Phosphatidylethanol 16:0/18:1, PEth). Self-reported lifetime abstinence, former drinking, current drinking, frequent drinking (≥4 times/week), and risk drinking (≥8 units/week) were measured. The PEth concentrations were stratified: <0.03 μmol/l (abstinence/very low level of alcohol consumption); >0.06 μmol/l (indicating >1 unit/day); >0.10 μmol/l (indicating >3 units/day), and >0.30 μmol/l (heavy alcohol consumption).

Results: In HUNT4, the prevalence of self-reported lifetime abstinence, frequent drinking, and risk drinking was 5.2%, 4.4%, and 5.6%, respectively, while prevalence of PEth <0.03 μmol/l was 68.1% and PEth >0.06 μmol/l was 21.2%. Over the course of the three surveys, the prevalence of self-reported lifetime abstinence decreased, while the prevalence of frequent drinking and risk drinking increased. Men were less often abstainers and more often frequent and risky drinkers than women in all three surveys. Gender differences for abstinence and current drinking reduced with time. From HUNT3 to HUNT4, the prevalence of PEth <0.03 μmol/l decreased, while the prevalence of PEth >0.06 μmol/l increased. Men compared to women, had less often PEth <0.03 μmol/l and more often PEth >0.06 and >0.10 μmol/l in HUNT3 and HUNT4. Women and men ≥75 years were just as likely to have PEth >0.30 μmol/l in HUNT4. The gender differences in PEth concentrations were reduced in HUNT4 among those aged 70-74 years or ≥75 years.

Conclusion: Alcohol consumption has increased among Norwegian older adults over a 24-year period, but at a slower pace during the last decade.

Kjerstin Tevik, Ragnhild Bergene Skråstad, Jūratė Šaltytė Benth, Geir Selbæk, Sverre Bergh, Rannveig Sakshaug Eldholm, Steinar Krokstad & Anne-Sofie Helvik

Introduction: Individuals with Alzheimer’s disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study’s goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.
Methods:
Genome-wide associationmeta-analysis of 9988 AD participants from six source studies with participants characterized for AD+PAD+A, and a joint phenotype (AD+A+P).
Results:
AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms.AD+Awas positively correlatedwith anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereasAD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations.
Discussion:
AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development.

Inga Margret Antonsdottir, Byron Creese, Lambertus Klei, Mary Ann A. DeMichele-Sweet, Elise A. Weamer, Pablo Garcia-Gonzalez, Marta Marquie, Mercè Boada, Emilio Alarcón-Martín,  Sergi Valero, NIA-LOAD Family Based Study Consortium, Alzheimer’s Disease Genetics Consortium (ADGC), AddNeuroMed Consortium, Yushi Liu, Basavaraj Hooli, Dag Aarsland, Geir Selbaek, Sverre Bergh, Arvid Rongve, Ingvild Saltvedt, Håvard K. Skjellegrind, Bo Engdahl, Ole A. Andreassen, Barbara Borroni, Patrizia Mecocci, Yehani Wedatilake, Richard Mayeux, Tatiana Foroud, Agustín Ruiz, Oscar L. Lopez, M. Ilyas Kamboh, Clive Ballard, Bernie Devlin, Constantine Lyketsos & Robert A. Sweet

Background: Demographic changes, with an increasing number and proportion of older people with multimorbidity and frailty, will put more pressure on home care services in municipalities. Frail multimorbid people receiving home care services are at high risk of developing crises, defined as critical challenges and symptoms, which demand immediate and new actions. The crises often result in adverse events, coercive measures, and acute institutionalisation. There is a lack of evidence-based interventions to prevent and resolve crises in community settings.

Methods: This is a participatory action research design (PAR) in a 6-month cluster randomised controlled trial (RCT). The trial will be conducted in 30 municipalities, including 150 frail community-dwelling participants receiving home care services judged by the services to be at risk of developing crisis. Each municipality (cluster) will be randomised to receive either the locally adapted TIME intervention (the intervention group) or care as usual (the control group). The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) is a manual-based, multicomponent programme that includes a rigorous assessment of the crisis, one or more interdisciplinary case conferences, and the testing and evaluation of customised treatment measures. PAR in combination with an RCT will enhance adaptations of the intervention to the local context and needs. The primary outcome is as follows: difference in change between the intervention and control groups in individual goal achievement to resolve or reduce the challenges of the crises between baseline and 3 months using the PRACTIC Goal Setting Interview (PGSI). Among the secondary outcomes are the difference in change in the PGSI scale at 6 months and in neuropsychiatric symptoms (NPSs), quality of life, distress perceived by professional carers and next of kin, and institutionalisation at 3 and 6 months.

Discussion: Through customised interventions that involve patients, the next of kin, the social context, and health care services, crises may be prevented and resolved. The PReventing and Approaching Crises for frail community-dwelling patients Through Innovative Care (PRACTIC) study will enhance innovation for health professionals, management, and users in the development of new knowledge and a new adapted approach towards crises.

Anette Væringstad, Ellen Thea Gjelseth Dalbak, Daniela Holle, Janne Myhre, Øyvind Kirkevold, Sverre Bergh & Bjørn Lichtwarck

Background: A timely diagnosis of dementia can be beneficial for providing good support, treatment, and care, but the diagnostic rate remains unknown and is probably low.

Objective: To determine the dementia diagnostic rate and to describe factors associated with diagnosed dementia.

Methods: This registry linkage study linked information on research-based study diagnoses of all-cause dementia and subtypes of dementias, Alzheimer’s disease, and related dementias, in 1,525 participants from a cross-sectional population-based study (HUNT4 70+) to dementia registry diagnoses in both primary-care and hospital registries. Factors associated with dementia were analyzed with multiple logistic regression.

Results: Among those with research-based dementia study diagnoses in HUNT4 70+, 35.6% had a dementia registry diagnosis in the health registries. The diagnostic rate in registry diagnoses was 19.8% among home-dwellers and 66.0% among nursing home residents. Of those with a study diagnosis of Alzheimer’s disease, 35.8% (95% confidence interval (CI) 32.6-39.0) had a registry diagnosis; for those with a study diagnosis of vascular dementia, the rate was 25.8% (95% CI 19.2-33.3) and for Lewy body dementias and frontotemporal dementia, the diagnosis rate was 63.0% (95% CI 48.7-75.7) and 60.0% (95% CI 43.3-75.1), respectively. Factors associated with having a registry diagnosis included dementia in the family, not being in the youngest or oldest age group, higher education, more severe cognitive decline, and greater need for help with activities of daily living.

Conclusions: Undiagnosed dementia is common, as only one-third of those with dementia are diagnosed. Diagnoses appear to be made at a late stage of dementia.

Linda Gjøra, Bjørn Heine Strand, Sverre Bergh, Ingunn Bosnes, Aud Johannessen, Gill Livingston, Håvard Kjesbu Skjellegrind & Geir Selbæk

Abstract

Deep learning approaches for clinical predictions based on magnetic resonance imaging data have shown great promise as a translational technology for diagnosis and prognosis in neurological disorders, but its clinical impact has been limited. This is partially attributed to the opaqueness of deep learning models, causing insufficient understanding of what underlies their decisions. To overcome this, we trained convolutional neural networks on structural brain scans to differentiate dementia patients from healthy controls, and applied layerwise relevance propagation to procure individual-level explanations of the model predictions. Through extensive validations we demonstrate that deviations recognized by the model corroborate existing knowledge of structural brain aberrations in dementia. By employing the explainable dementia classifier in a longitudinal dataset of patients with mild cognitive impairment, we show that the spatially rich explanations complement the model prediction when forecasting transition to dementia and help characterize the biological manifestation of disease in the individual brain. Overall, our work exemplifies the clinical potential of explainable artificial intelligence in precision medicine.

Esten H. Leonardsen, Karin Persson, Edvard Grødem, Nicola Dinsdale, Till Schellhorn, James M. Roe, Didac Vidal-Piñeiro, Øystein Sørensen, Tobias Kaufmann, Eric Westman, Andre Marquand, Geir Selbæk, Ole A. Andreassen, Thomas Wolfers, Lars T. Westlye & Yunpeng Wang