Forskningsartikler

Abstract

Background/aims: The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score.

Methods: MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E ɛ4 (APOE ɛ4) carrier status.

Results: Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses.

Conclusion: The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms.

Rachel Amland, Geir Selbæk, Anne Brækhus, Trine H. Edwin, Knut Engedal, Anne-Brita Knapskog, Ellen Regine Olsrud, & Karin Persson

Abstract

Background: High blood pressure and poor cardiorespiratory fitness are independent risk factors for dementia. However, few studies have examined if combined longitudinal patterns of these modifiable risk factors are associated with dementia risk.

Methods: In this prospective cohort study, we used data from the population-based HUNT Study, Norway. We applied group-based multidimensional trajectory modeling to identify age-specific multidimensional trajectories of SBP, DBP and estimated cardiorespiratory fitness across three surveys (HUNT1, 1984-86 – HUNT3, 2006-08). Dementia was diagnosed in the HUNT4 70+ substudy in 2017-19. We used multivariate logistic regression to estimate odds ratios (ORs) and risk differences (RDs) of dementia.

Results: In total, 7594 participants (54.9% women) were included, with a mean age of 44.7 (SD 6.3) years at HUNT1. Dementia was diagnosed in 1062 (14.0%) participants. We identified two multidimensional trajectories throughout adulthood within three age groups: one with higher SBP and DBP, and lower estimated cardiorespiratory fitness (the poorer group), and one with lower SBP and DBP, and higher cardiorespiratory fitness (the better group). After adjustment for sex, APOE ε4 status, education, marital status and diabetes, the better group had consistently lower risk of dementia in all age groups with the lowest OR in the middle-aged group of 0.63 (95% CI 0.51, 0.78) with corresponding RD of -0.07 (95% CI -0.10, -0.04).

Conclusions: Having a beneficial multidimensional trajectory of SBP, DBP and cardiorespiratory fitness in adulthood was associated with reduced dementia risk. Aiming for optimal SBP, DBP and estimated cardiorespiratory fitness throughout adulthood may reduce dementia risk.

Maren Lerfald, Heather Allore, Tom I L Nilsen, Rannveig S Eldholm, Nicolas Martinez-Velilla, Geir Selbæk & Linda Ernstsen

Abstract

Purpose: Coronavirus disease 2019 (COVID-19) placed a significant strain on nursing homes, leading to numerous outbreaks and high mortality rates. This situation created considerable stress and challenges for residents, their physicians and nurses, as well as family caregivers. By understanding these challenges, we can gain new insights and learn valuable lessons. Thus, the purpose of this study is to examine the treatment and care provided to nursing home residents with COVID-19, as experienced by physicians, nurses, and family caregivers.

Participants and Methods: This study is a secondary analysis of 35 interviews with physicians, nurses, and family caregivers, each with personal experience caring for nursing home residents diagnosed with COVID-19. The interviews took place from December 2020 to April 2021. We analyzed the transcriptions based on Braun and Clarke’s reflexive thematic analysis model and followed a qualitative descriptive design as outlined by Sandelowski.

Findings: The analysis produced three themes: 1) Balancing medical treatment, 2) The need for increased systematic monitoring of vital functions, and 3) Determining the treatment level for nursing home residents. These themes were explored through the unique perspectives of the three participant groups: physicians, nurses, and family caregivers. The findings revealed several challenges related to treatment and care for nursing home residents diagnosed with COVID-19. This applied both to relief of symptoms, monitoring of vital functions, assessment of treatment level and use of advance care planning.

Conclusion: Drawing from the experiences of physicians, nurses, and family caregivers, there should be a unified plan at the municipal or national level for competency development in nursing homes to prepare for future crises like pandemics or epidemics. Additionally, the safe engagement of family caregivers and relatives should be given priority.

Anita Nilsen, Siren Eriksen, Bjørn Lichtwarck, Adelheid Hummelvoll Hillestad, Signe Gunn Julnes, Signe Tretteteig & Anne Marie Mork Rokstad

Abstract
Spousal bereavement is associated with health declines and increased mortality risk, but its specific impact on physical and cognitive capabilities is less studied. A historical cohort study design was applied including married Tromsø study participants (N=5739) aged 50-70 years with baseline self-reported overall health and health-related factors and measured capability (grip strength, finger tapping, digit symbol coding, and short-term recall) at follow-up. Participants had data from Tromsø4 (1994-1995) and Tromsø5 (2001), or Tromsø6 (2007-2008) and Tromsø7 (2015-2016). Propensity score matching, adjusted for baseline confounders (and baseline capability in a subset), was used to investigate whether spousal bereavement was associated with poorer subsequent capability. Spousal bereavement occurred for 6.2% on average 3.7 years (SD 2.0) before the capability assessment. There were no significant bereavement effects on subsequent grip strength, immediate recall, or finger-tapping speed. Without adjustment for baseline digit symbol coding test performance, there was a negative significant effect on the digit symbol coding test (ATT -1.33; 95% confidence interval -2.57, -0.10), but when baseline digit symbol coding test performance was taken into account in a smaller subsample, using the same set of matching confounders, there was no longer any association (in the subsample ATT changed from -1.29 (95% CI -3.38, 0.80) to -0.04 (95% CI -1.83, 1.75). The results in our study suggest that spousal bereavement does not have long-term effects on the intrinsic capacity components physical or cognition capability to a notable degree.

Bjørn Heine Strand, Asta K Håberg, Harpa Sif Eyjólfsdóttir, Almar Kok, Vegard Skirbekk, Oliver Huxhold, Gøril Kvamme Løset, Carin Lennartsson, Henrik Schirmer, Katharina Herlofson, Marijke Veenstra

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