Forskningsartikler

Background: There are several subtypes of dementia caused by different pathophysiology and with different clinical characteristics. Irrespective subtype, the disease is progressive, eventually leading to the need for care and supervision on a 24/7 basis, often provided in nursing homes (NH). The progression rate and course of the disease might vary according to subtype. The aim of this study was to explore whether the mortality rate for NH residents varied according to the subtype of dementia.

Methods: NH residents were followed from admission to NH over a period of 36 months or until death with annual follow-up examinations. Demographic and clinical data were collected. The diagnosis of dementia and its subtype at baseline (BL) were set according to international accepted criteria. Kaplan-Meier analysis was performed to estimate median survival time. A Cox regression model was estimated to assess the impact of dementia diagnosis and demographic and clinical variables on mortality.

Results: A total of 1349 participants were included. When compared to persons with Alzheimer’s disease (AD), persons with frontotemporal dementia (FTD) and dementia with Lewy bodies or Parkinson’s disease dementia (DLB/PDD) were younger and had more neuropsychiatric symptoms. Median survival for the total sample was 2.3 years (95% confidence interval: 2.2–2.5). When compared to persons with AD, having no dementia or unspecified dementia was associated with higher mortality, while we found similar mortality in other subtypes of dementia. Higher age, male gender, poorer general health, higher dependency in activities of daily living, and more affective symptoms were associated with higher mortality.

Conclusion: Mortality did not differ across the subtypes of dementia, except in persons with unspecified dementia or without dementia, where we found a higher mortality. With a median survival of 2.3 years, NH residents are in the last stage of their lives and care and medical follow-up should focus on a palliative approach. However, identifying the subtype of dementia might help carers to better understand and address neuropsychiatric symptoms and to customize medical treatment.

Corinna Vossius, Sverre Bergh, Geir Selbæk, Jūratė Šaltytė Benth, Janne Myhre, Eivind Aakhus & Bjørn Lichtwarck

Introduction: One pathological hallmark of Alzheimer’s disease (AD) is atrophy of medial temporal brain regions that can be visualized on magnetic resonance imaging (MRI), but not all patients will have atrophy. The aim was to use MRI to categorize patients according to their hippocampal atrophy status and to present prevalence of the subtypes, difference in clinical symptomatology and progression, and factors associated with hippocampal subtypes.

Methods: We included 215 patients with AD who had been assessed with the clinically available MRI software NeuroQuant (NQ; CorTechs labs/University of California, San Diego, CA, USA). NQ measures the hippocampus volume and calculates a normative percentile. Atrophy was regarded to be present if the percentile was ≤5. Demographics, cognitive measurements, AD phenotypes, apolipoprotein E status, and results from cerebrospinal fluid and amyloid positron emission tomography analyses were included as explanatory variables of the hippocampal subtypes.

Results: Of all, 60% had no hippocampal atrophy. These patients were younger and less cognitively impaired concerning global measures, memory function, and abstraction but impaired concerning executive, visuospatial, and semantic fluency, and more of them had nonamnestic AD, compared to those with hippocampal atrophy. No difference in progression rate was observed between the two groups. In mild cognitive impairment patients, amyloid pathology was associated with the no hippocampal atrophy group.

Conclusion: The results have clinical implications. Clinicians should be aware of the large proportion of AD patients presenting without atrophy of the hippocampus as measured with this clinical MRI method in the diagnostic set up and that nonamnestic phenotypes are more common in this group as compared to those with atrophy. Furthermore, the findings are relevant in clinical trials.

Karin Persson, Trine H Edwin, Anne-Brita Knapskog, Gro G Tangen, Geir Selbæk, Knut Engedal

Background
Behavioral and psychological symptoms of dementia (BPSD) occur frequently in people with dementia and can contribute to an increased need for help and a reduced quality of life, but also predict early institutionalization. The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) might be a useful personalized approach to BPSD in people with dementia. The main objective of this feasibility trial was to explore the trial design and methods along with the patients’ and the home care staff’s acceptance of the TIME intervention before developing a definitive trial. Additionally, we wanted to explore whether TIME could be appropriate for staff in home care services in their approach towards people with dementia with anxiety and depression.

Methods
This was a 18-month feasibility trial using a parallel cluster randomized controlled design. Nine municipalities from the eastern part of Norway (clusters) — 40 people with dementia and 37 of their next of kin— were randomized to the TIME intervention or to treatment as usual. In addition, qualitative data as field notes were collected and summarized.

Results
The staff in home care services experienced TIME as an appropriate method; in particular, the systematic approach to the patient’s BPSD was experienced as useful. However, the completion of the assessment phase was considered exhaustive and time-consuming, and some of the staff found it challenging to find time for the case conferences.

Conclusions
We consider that TIME, with some adjustments, could be useful for staff in home care services in cases where they face challenges in providing care and support to people with dementia. This feasibility trial indicates that we can move forward with a future definitive randomized controlled trial (RCT) to test the effect of TIME in people with dementia receiving home care services

Kari-Anne Hoel, Bjørn Lichtwarck, Anette Væringstad, Ingvild Hjorth Feiring, Anne Marie Mork Rokstad, Geir Selbæk, Jūratė Šaltytė Benth, Sverre Bergh

Background: Drugs commonly prescribed for heart rate control may induce adverse drug reactions in Alzheimer patients treated with acetylcholinesterase inhibitors (AChEIs). We have studied use of drugs with a known risk of Torsades de pointes (TdP) and drugs used to treat behavioral and psychological symptoms of dementia, as well as a combination of drugs with a known risk of TdP and drugs with a known heart rate-lowering effect, before and after initiating treatment with AChEIs.

Methods: The study applied data from the Norwegian Prescription Database for the period 2004–2016. Prescriptions of concomitant use of drugs in persistent users of AChEIs was studied in a follow-up period from 4 years before to 2 years after AChEI initiation in men and women of two age groups: 37–80 and 81–88 years.

Results: A small number of patients were prescribed haloperidol (∼1.5% The second year after AChEI initiation), digoxin/digitoxin (∼3%), and verapamil (∼1.3%), while a substantial proportion of the patients were prescribed betablockers (∼28%) and citalopram/escitalopram (∼17%). During follow-up, up to 6% of the study population were prescribed both betablockers and citalopram/citalopram in addition to AChEIs, a combination that increased over the follow-up period and was observed most frequently in women in the oldest age group.

Conclusions: A large proportion (∼44%) of patients treated with AChEIs were prescribed drugs that could cause bradycardic and prolonged time from the start of the Q wave to the end of the T wave (QT interval). Thus, action should be taken to reduce the combination of drugs with risk of bradycardia and prolonged QT interval. Medication review on a regular basis could be an option as an important risk-reducing intervention.

Anne Sverdrup Efjestad, Hege Ihle-Hansen, Vidar Hjellvik, Knut Engedal, Hege Salvesen Blix

Purpose
The lack of epidemiological data on the proportion of olfactory dysfunction (OD) using comprehensive olfactory assessment in healthy adults in Scandinavia motivated to the present study which aimed to explore the proportion of OD in voluntary healthy Norwegian adults, assessed by Sniffin’ Sticks, and its correlation to self-reported olfactory function. Furthermore, sociodemographic and clinical factors associated with olfactory function were analysed.
Methods
The sample included 405 Norwegian participants, aged 18–78 years, 273 women and 132 men, who underwent olfactory testing with extensive Sniffin’ Sticks test, allergy testing, clinical examination with nasal endoscopy and completed a self-administered questionnaire, including self-evaluation of olfactory function on a 100 mm Visual Analogue Scale.
Results
We found that 37% had OD, of which 1.2% had anosmia assessed with extensive Sniffin’ Sticks test. The proportion of hyposmia and anosmia increased with age. Men and participants with low education had poorer olfactory function scores. Allergy, smoking status, general health and endoscopic findings were not associated with measured olfactory function. We found no correlation between self-reported and measured olfactory function.
Conclusions
This study has identified that a large proportion of our sample of voluntary healthy Norwegian adults have OD, considerably more common in older adults and somewhat more common in men and individuals with low education. The lack of correlation between self-reported and measured olfactory function highlights the importance of using validated tests for a reliable olfactory evaluation.

Ingrid Torvik Heian, Anne-Sofie Helvik, Thomas Hummel, Marte Rystad Øie, Ståle Nordgård, Mette Bratt, Wenche Moe Thorstensen

Abstract: Authorities and research institutions emphasise and encourage interdisciplinary research to meet complex societal health challenges as dementia. However, studies that describe an interdisciplinary approach for dementia research are limited. What does it take for research to become interdisciplinary? Is it enough to include researchers from different disciplines? This paper reflects on an interdisciplinary approach to dementia research. Based on existing literature and theories, we elaborate the concept of interdisciplinarity, and how the perspective can contribute and improve dementia care.

Tanja Louise Ibsen, Siren Eriksen

Background: Vitamin D insufficiency has been suggested as a dementia risk factor.

Objective: In this cross-sectional, explorative study we investigated whether levels of vitamin D in cerebrospinal fluid (CSF) are lower in patients with positive biomarkers of Alzheimer’s disease (AD) compared to cognitively healthy controls and whether polymorphisms of the vitamin D receptor (VDR) gene, FokI, BsmI, ApaI, and TaqI, are associated with levels of vitamin D in CSF and cognition.
Methods: We included 100 patients≥65 years assessed for cognitive impairment and 76 cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D) in both serum and CSF, and VDR polymorphisms were analyzed.
Results: The mean level of 25(OH)D in serum was 78.6 (SD 28.9) nmol/l. While serum levels of 25(OH)D were not significantly different between the groups, CSF levels of 25(OH)D were significantly lower in patients with positive AD core biomarkers (p = 0.001) compared to patients without such biomarkers. Individuals with the BsmI major homozygote genotype had significantly lower results on a 10-word delayed recall test (p = 0.044) and verbal fluency test (p = 0.013), and individuals with the TaqI major homozygote genotype had significantly lower results on a verbal fluency test (p = 0.030) compared to individuals with the corresponding minor homozygote genotype.

Conclusion: Patients with positive AD core biomarkers have low CSF levels of 25(OH)D, despite sufficient serum levels. CSF levels of 25(OH)D do not seem to be affected by any of the four VDR gene polymorphisms. TaqI and BsmI major homozygote genotypes might be at increased risk for development of cognitive decline.

Jelena Zugic Soares, Jørgen Valeur, Jūratė Šaltytė Benth, Anne-Brita Knapskog, Geir Selbæk, Golchin Arefi, D Gregor Gilfillan, Anita Tollisen, Nenad Bogdanovic, Renate Pettersen

Background: As in other countries, the COVID-19 pandemic has affected Norway’s immigrant population disproportionately, with significantly higher infection rates and hospitalisations. The reasons for this are uncertain.
Methods: Through the national emergency preparedness register, BeredtC19, we have studied laboratory-confirmed infections with SARS-CoV-2 and related hospitalisations in the entire Norwegian population, by birth-country background for the period 15 June 2020 to 31 March 2021, excluding the first wave due to limited test capacity and restrictive test criteria. Straightforward linkage of individual-level data allowed adjustment for demographics, socioeconomic factors (occupation, household crowding, education and household income), and underlying medical risk for severe COVID-19 in regression models.
Results: The sample comprised 5.49 million persons, of which 0.91 million were born outside of Norway, there were 82,532 confirmed cases and 3088 hospitalisations. Confirmed infections in this period (per 100,000): foreign-born 3140, Norwegian-born with foreign-born parents 4799 and Norwegian-born with Norwegian-born parent(s) 1011. Hospitalisations (per 100,000): foreign-born 147, Norwegian-born with foreign-born parents 47 and Norwegian-born with Norwegian-born parent(s) 37. The addition of socioeconomic and medical factors to the base model (age, sex, municipality of residence) attenuated excess infection rates by 12.0% and hospitalisations by 3.8% among foreign-born, and 10.9% and 46.2%, respectively, among Norwegian-born with foreign parents, compared to Norwegian-born with Norwegian-born parent(s).

Conclusions: There were large differences in infection rates and hospitalisations by country background, and these do not appear to be fully explained by socioeconomic and medical factors. Our results may have implications for health policy, including the targeting of mitigation strategies.

Angela S Labberton, Anna Godøy, Ingeborg Hess Elgersma, Bjørn Heine Strand, Kjetil Telle, Trude Arnesen, Karin Maria Nygård, Thor Indseth

Background: The effect of the Norwegian General Practice–Nursing Home (NorGeP–NH) criteria has never been tested on clinical outcomes in nursing home (NH) residents. We performed a cluster-randomized trial in Norwegian NHs and tested the effect of NorGeP–NH on QoL (primary outcome), medication prescriptions, and physical and mental health (secondary outcomes) for the enrolled residents;
Methods: Fourteen NHs were randomized into intervention NHs (iNHs) and control NHs (cNHs). After baseline data collection, physicians performed NorGeP–NH on the enrolled residents. We assessed the difference between cNHs and iNHs in the change in primary outcome from baseline to 12 weeks and secondary outcomes from baseline to eight and 12 weeks by linear mixed models; Results: One hundred and eight residents (13 lost to follow-up) and 109 residents (nine lost to follow-up) were randomized to iNHs and cNHs, respectively. Difference in change in QoL at 12 weeks between cNHs and iNHs was not statistically significant (mean (95% CI)): −1.51 (−3.30; 0.28), p = 0.101). We found no significant change in drug prescriptions over time. Difference in depression scores between cNHs and iNHs was statistically significant after 12 weeks.
Conclusions:
Our intervention did not affect QoL or drug prescriptions, but reduced depression scores in the iNHs. NorGeP–NH may be a useful tool, but its effect on clinical outcomes may be scarce in NH residents. Further studies about the effectiveness of NorGeP–NH in other healthcare contexts and settings are recommended.

Enrico Callegari, Jurate Šaltytė Benth, Geir Selbæk, Cato Grønnerød and Sverre Bergh