Forskningsartikler

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

A registered report protocol

Abstract

Background: People with cognitive impairment frequently have multiple comorbidities, and polypharmacy is highly prevalent, affecting nearly half of individuals with mild cognitive impairment and dementia. The use of potentially inappropriate medications (PIMs), including those specifically problematic for cognitive impairment (PIMcog), increases with the total number of medications and may exacerbate cognitive symptoms or increase the risk of adverse drug events. However, the prevalence of polypharmacy and PIMcog use among patients diagnosed with MCI or dementia in Norwegian specialist outpatient clinics has not been described.

Methods: We will conduct a retrospective cohort study linking national health registries to estimate the prevalence of polypharmacy and PIMcog use in the year prior to diagnosis of mild cognitive impairment or dementia. Data from the Norwegian Registry of Persons Assessed for Cognitive Symptoms will be linked to dispensing data from the Norwegian Prescribed Drug Registry and comorbidity data from the Norwegian Patient Registry. The study population will include all patients diagnosed with mild cognitive impairment or dementia in Norwegian specialist outpatient clinics from 2014 to 2024. We will estimate the twelve-month prevalence of polypharmacy and PIMcog use preceding diagnosis, compare sociodemographic and clinical characteristics between PIMcog users and non-users, and identify factors associated with PIMcog use.

Expected impact: By describing the one-year prevalence and patterns of polypharmacy and PIMcog use and associated factors prior to mild cognitive impairment and dementia diagnosis, the findings may inform targeted deprescribing interventions and safer prescribing strategies for individuals with cognitive impairment.

Hege Kersten, Tonje Marie Bø Vaksvik, Rita Romskaug, Torgeir Bruun Wyller, Keson Jaioun, Edoardo Botteri, Geir Selbæk

Abstract

BackgroundStudies have shown that the performance on the Clock Drawing Test (CDT) is influenced by age and education. Thus, normative scores are needed.ObjectiveTo develop normative Norwegian scores for Shulman’s version of CDT.MethodsPerformance on CDT of 2572 cognitively healthy people between age 25 and 95 years were included. Ordinal regression analysis was used to derive regression-based norms with sex, age and education as covariates.ResultsOf all, 76.4% scored five, 12.9% scored four, 8.1% scored three and 2.5% scored zero to two. Men scored higher than women. An interaction between age and education was found. The probability of higher CDT score is highest at younger ages and among those with highest education. It progressively declines with increasing age, while higher education delays, but does not prevent this decline. Participants scoring zero to two fell below the 5th percentile, except among women above 93 years and men above 85 years. By age 95, the probability of different scores converged. In the age range of 60 to 90 years a score of three corresponded to percentiles of 3.7-26.9 in men and 5.2-34.1 in women, while a score of four corresponded to percentiles of 9.7-50.4 in men and 13.2-59.0 in women.ConclusionsScores four and five are considered normal for any person aged 60-90 years. Whether a score of three is normal depends on the person’s sex, age and educational level, whereas score zero to two should not be regarded as normal.

Knut Engedal, Jūratė Šaltytė Benth, Anne-Brita Knapskog, Jørgen Wagle, Karin Persson

Abstract

Aims and objectives: To explore the experiences of receiving and living with a diagnosis of prodromal Alzheimer’s disease.

Background: Alzheimer’s disease is a progressive dementia disorder, with pathology potentially developing years before clinical symptoms. Evidence concerning patients’ perspectives on living with a prodromal Alzheimer’s disease diagnosis remains scarce.

Design and methods: A qualitative, descriptive design was employed. Semi-structured interviews were conducted with 16 participants diagnosed with prodromal Alzheimer’s disease in memory clinics in Denmark, Norway and Iceland. The data were analysed using thematic analysis.

Findings: Four main themes emerged: 1) what led to the assessment, 2) receiving the diagnosis of prodromal Alzheimer’s disease, 3) everyday life after the diagnosis and 4) planning for the future. The participants experienced diverse trajectories to diagnosis, with some being alerted by others to symptoms and some recognising the symptoms themselves. The diagnostic process was often perceived as intimidating, and person-centred care was valued. After the diagnosis, the participants focused on managing daily life, experienced changes in relationships and harboured mixed emotions about the future.

Conclusion: Receiving a prodromal Alzheimer’s disease diagnosis impacts patients’ perceptions of their abilities, relationships and future. There is a need for interventions targeting both patients and their families to maintain a close bond between them and support hope. Clear communication about the distinction between prodromal Alzheimer’s disease and Alzheimer’s dementia is crucial.

Susanne Kristiansen, Siren Eriksen, Cathrine Selnes Treviño, Tarja Välimäki, Helga Atladóttir, Gudlaug Gudmundsdottir, Knut Engedal, Jón Snædal, Anne Marie Mork Rokstad, Hanne Konradsen

Abstract

High blood pressure (BP) is linked to an increased dementia risk. The role of sex and the impact of cardiorespiratory fitness (CRF) on the potential association between genetic predisposition to high blood pressure and dementia are less understood. Our aim was to investigate if there is an association between genetic predisposition to high systolic blood pressure (SBP) and occurrence of dementia in males and females and whether CRF modifies this association. This prospective cohort study utilised data from the population-based Trøndelag Health Study in Norway. We included 9145 participants ≥70 years in the HUNT4 70+ sub-study. The sex-specific association between the BP polygenic score (PGS) and dementia was estimated by logistic regression. Analyses were stratified by CRF to investigate potential effect modification by CRF. Among 5011 females (mean age 78.5 years) and 4134 males (mean age 77.4 years), 812 (16.2%) and 570 (13.8%) dementia cases were identified, respectively. Females in the highest fifth of the PGS had an increased odds of dementia [odds ratio (OR) = 1.45; 95% confidence interval (CI) 1.10 to 1.90]. This was not observed in males (OR = 1.03; 95% CI 0.77 to 1.37). The association was somewhat stronger in females with low fitness (OR = 1.53; 95% CI 1.08 to 2.17) than in females with high fitness (OR = 1.12; 95% CI 0.78 to 1.63). Genetic predisposition to high SBP was associated with higher odds of dementia in females, particularly if they had low CRF. Future studies should further examine sex-specific effects of genetic and modifiable factors on dementia risk.

Maren Lerfald, Karsten Øvretveit, Tom Ivar Lund Nilsen, Rannveig Sakshaug Eldholm, Nora Grøtting, Brooke N Wolford, Geir Selbaek, Linda Ernstsen

Abstract

Background and objectives: Central and general adiposity have been linked to dementia risk, but their relation to blood-based Alzheimer disease (AD) biomarkers is unclear. We examined life course adiposity, measured by waist-to-height ratio (WtHR) and body mass index (BMI), in relation to plasma p-tau217 and to AD dementia verified by biomarker status.

Methods: In this cohort study, we included data on participants from the general population aged 70 years or older from the fourth wave of the Norwegian Trøndelag Health Study (HUNT4; 2017-19). Plasma p-tau217 was collected and standardized clinical cognitive assessments were performed at HUNT4. Plasma p-tau217 concentration at ≥0.63 pg/mL defined positive p-tau217. Positive p-tau217 coupled with a clinical dementia diagnosis defined biomarker-verified AD dementia. WtHR was measured 3 times (HUNT2-4; 1995-2019), and BMI was measured 4 times (HUNT1-4; 1984-2019). We performed linear, logistic, and linear mixed-effects regression adjusting for demographics, APOE ε4, lifestyle, and mental health.

Results: The final study sample comprised 8,797 participants (53.5% women, mean age at HUNT4 77.8 [SD 6.2]). Of these, 2,649 (30.1%) were p-tau217-positive and 659 (7%) had biomarker-verified AD dementia. Midlife WtHR ≥0.60 was associated with 12.8% (95% CI 7.3-19.7) higher late-life p-tau217 concentration and higher risk of positive p-tau217 (relative risk ratios [RRRs] 1.55, 1.21-1.99) and biomarker-verified AD dementia (RRR 1.84, 1.27-2.65) compared with WtHR <0.50. In late life, WtHR ≥0.60 was associated with 15.6% (-19.0 to -12.2) lower p-tau217 concentration and lower risk of positive p-tau217 (RRR 0.49, 0.41-0.59) and biomarker-verified AD dementia (RRR 0.63, 0.46-0.86). BMI showed similar patterns: Midlife obesity was associated with higher p-tau217 concentration and elevated risk of biomarker-verified AD dementia, whereas late-life overweight/obesity was associated with lower p-tau217 and decreased risk of biomarker-verified AD dementia. Among those with positive p-tau217 or biomarker-verified AD dementia, mixed-effects regression showed higher midlife adiposity, reversing by late life.

Discussion: Our results identify midlife central and general adiposity as modifiable risk factors for AD pathology and AD dementia. WtHR may aid early risk stratification and inform interventions targeting central fat reduction.

Ekaterina Zotchev, Bjørn Heine Strand, Anita Sunde, Kay Deckers, Dag Aarsland, Nicholas J Ashton, Henrik Zetterberg, Vegard Fykse Skirbekk, Miguel G Borda, Gill Livingston, Archana Singh-Manoux, Geir Selbaek

Abstract
Background: Adults with Down syndrome (DS) have a high dementia risk, highlighting the need for robust, DS-specific assessment tools. This study evaluated the psychometric properties of the Norwegian version of the CAMDEX-DS-II by examining reliability and validity of the informant interview and the CAMCOG-DS-II cognitive assessment.

Method: In this nationwide study, 108 adults with DS were assessed across 19 hospital units during 2021-2023. Participants underwent a standardised dementia assessment including the CAMDEX-DS-II battery. Reliability was assessed using Cronbach’s alpha, weighted kappa, and intraclass correlation coefficients (ICCs), while validity was evaluated using factor analysis, receiver operating characteristic (ROC) analyses, and external cognitive and functional measures.

Results: The CAMDEX-DS-II informant interview demonstrated good to excellent psychometric properties, with high internal consistency (α ≥ 0.83) in core cognitive-functional sections and strong inter-rater reliability, with most items showing excellent weighted kappa (κ ≥ 0.80). Scores aligned closely with clinician-determined diagnostic classifications. The CAMCOG-DS-II showed very good internal consistency (α = 0.84) and excellent inter-rater reliability (ICCs ≥ 0.90). CAMCOG-DS-II total and domain scores differed significantly across diagnostic groups, with moderate-to-large effect sizes. ROC analyses indicated good overall diagnostic accuracy, with areas under the curve (AUCs) > 0.80, and particularly strong discrimination in individuals with mild ID.

Conclusions: The Norwegian CAMDEX-DS-II provides reliable indicators of dementia-related change in adults with DS. The combined informant interview and cognitive assessment provided evidence based on relations to diagnostic classification and external measures, supporting their clinical utility in the specialist services and contributing to the international evidence base.

Frode Kibsgaard Larsen, Ingrid Tøndel Medbøen, Andre Strydom, Geir Selbæk, Bjørn Heine Strand, Ellen Melbye Langballe

Abstract

Apolipoprotein E (APOE) genotype and cardiovascular risk are both associated with dementia, but their separate and joint contributions remain uncertain. We examined the independent and combined associations of APOE genotype and cardiovascular disease (CVD) risk with incident dementia in a Norwegian populationbased cohort. In this prospective cohort study, baseline data were obtained from the second Trøndelag Health Study (HUNT2, 1995–97), with follow-up through linkage to specialist health-care records and the Norwegian Cause of Death Registry through Dec 31, 2023. We included 22,108 participants aged 50 years or older who were free of CVD, diabetes, and dementia at baseline. APOE genetic risk and cardiovascular risk based on SCORE2 were each classified into three categories. Adjusted hazard ratios (HRs) for incident dementia were estimated using Cox models. During a median follow-up of 22.0 years, 3,714 incident dementia events occurred. Compared with low APOE genetic risk, adjusted HRs were 1.25(95% CI1.10–1.41) for intermediate risk and 3.09(2.73–3.49) for high risk. Compared with low-to-moderate CVD risk, adjusted HRs were 1.19(1.07–1.32) for high risk and 1.36(1.19–1.55) for very high risk. In joint analyses, the highest risk was observed in participants with high APOE genetic risk and very high cardiovascular risk (HR 3.78, 2.85–5.01). Higher cardiovascular risk was more clearly associated with dementia in participants without high APOE genetic risk, whereas dementia risk was consistently There was no clear evidence of multiplicative interaction (p=0.059). APOE genotype and cardiovascular risk were independently associated with incident dementia, with highest risk among individuals with both high genetic and cardiovascular risk.

Nora Grøtting, Brooke N. Wolford, Kirsti Kvaløy, Torbjørn Omland, Geir Selbæk & Linda Ernstsen

Abstract

ULK1 (Atg1) initiates macroautophagy and mitophagy, which support neuronal growth and survival, yet how this pathway is disrupted in aging and Alzheimer’s disease (AD) remains unclear. Here we report reduced ULK1 in serum and cerebrospinal fluid during aging in cognitively unimpaired participants from the COGNORM study (n = 75) and in patients with AD from the NorCog Memory Clinic Cohort (n = 316). In AD mice, ULK1 overexpression stimulates autophagic flux, reduces AD pathology and delays cognitive decline alongside increased phagocytic degradation of amyloid-β, reduced tauopathy and improved mitochondrial quality. Mechanistically, ULK1 upregulation increases autophagy and PINK1-, FUNDC1- and AMBRA1-associated mitophagy; higher autophagy and mitophagy increase cellular NAD+, which in turn deacetylates acetylated-Tau174 via the NAD+–SIRT1 axis, leading to reduced tauopathy. Using in vitro tau seeding assays and a Caenorhabditis elegans tau model, we validate the efficacy of ULK1 activators in inhibiting tauopathy. We propose that age-related decline in ULK1 leads to autophagy and mitophagy impairment and increases the progression of AD and identify ULK1 as a potential therapeutic target.

Jun-Ping Pan  (潘君平), Ping-Jie Wang  (王平洁), Jianying Zhang  (张剑英), Anne-Brita Knapskog, Leiv Otto Watne, He-Ling Wang  (王鹤龄), Maria Jose Lagartos-Donate, Sofie Lautrup, Li-Peng Mao  (茅立鹏), Qian Wang  (王倩), Zhi-Peng Ling  (凌志鹏), Shi-qi Zhang  (张诗琦), Tomás Schmauck-Medina, Ruixue Ai  (艾瑞雪), Trine Holt Edwin, Tianjiao Zhang  (张天娇), Ingvild Saltvedt, Rannveig Sakshaug Eldholm, Annabel Smith, Kateřina Veverová, Domenica Caponio, Asgeir Kobro-Flatmoen, Huanhuan Pang  (庞欢欢), Zijian Wang  (王子健), Haoyun Wang  (王昊云), Li-juan Gao  (高利娟), Nathalie Bodd Halaas, Garry Wong, Martin Vyhnalek, Oscar Junhong Luo  (罗钧洪), William A. McEwan, Jon Storm-Mathisen, Li Gan, Zeping Hu  (胡泽平), Henrik Zetterberg, Menno P. Witter, Dag Aarsland, Geir Selbæk, Guobing Chen  (陈国兵) & Evandro Fei Fang  (方飛)