Forskningsartikler

Background: The 2024 Lancet Commission report on dementia identified 14 modifiable dementia risk factors. The Norwegian HUNT study uniquely includes data collection of all 14 risk factors in the same individuals throughout adulthood, as well as a study-specific dementia diagnosis. We aimed to evaluate the potential for dementia prevention associated with these 14 risk factors, along with three additional sociodemographic risk factors in this retrospective cohort.

Methods: This retrospective cohort study included data on participants with study-specific diagnosis from the HUNT4 70+ study (2017-19) and was linked with national administrative registries (1960-2018) and earlier HUNT surveys (1984-2008) with data on dementia risk factors at ages 35-92 years. Inverse probability weighting was applied to account for non-response. Logistic regression estimated dementia risk associated with exposure to less education in early adult life (age <45 years), hearing loss, high LDL cholesterol, depression, traumatic brain injury, physical inactivity, diabetes, smoking, hypertension, obesity, excessive alcohol use in midlife (age 45-65 years), and social isolation, air pollution, and vision loss in late life (age >65 years). Midlife occupational physical activity and marital and employment status were added to the Lancet model. The potential for dementia prevention was assessed using population attributable fraction (PAF).

Findings: Between Sept 1, 2017, and Feb 28, 2019, 19 403 individuals were invited to participate and 9745 participants (1525 with dementia, 8220 without dementia) were included. 4445 (45·6%) of 9745 participants were male and 5300 (54·4%) were female. The total PAF for the 14 Lancet risk factors was 50·9% (95% CI 37·7-61·4). Including family-related and work-related risk factors increased the PAF to 54·9% (42·3-64·7; p<0·0001). When these factors were added for women, the total PAF increased from 48·0% (95% CI 29·4-61·7) to 52·2% (34·2-65·3; p=0·0090), whereas no significant change was observed in men (56·2% [95% CI 35·5-70·2] to 56·7 [95% CI 36·1-70·6]; p=0·71).

Interpretation: Addressing all 14 Lancet risk factors could prevent over half of all dementia cases. Adding factors related to marital and occupational status offers additional preventive potential, particularly among women.

Merete Ellingjord-Dale, Bjørn Heine Strand, Vegard Skirbekk, Bernt Bratsberg, Teferi Mekonnen, Ekaterina Zotcheva, Geir Selbæk, Yaakov Stern, Asta Kristine Håberg, Bo Engdahl

Background
Smoking is considered a risk factor for dementia. Nevertheless, uncertainty regarding the associations with dementia subtypes and the effects of quitting remains. In this large longitudinal population-based cohort study, we investigated smoking as an independent risk factor for all-cause dementia. Second, we investigated the associations with dementia subtypes.

Methods
We included participants from the Trøndelag Health Study (HUNT) and collected their smoking status at baseline (HUNT2, 1995-97). We assessed cognitive status at follow-up two decades later (HUNT4 70+, 2017-19, N = 8,532) and collected pack-years. We handled missing data with multiple imputations and estimated relative risks (RRs) with Poisson regression after adjustment for covariates and stratification by age and sex.

Results
Current smokers had a 31% increased dementia risk (RR 1.31, 95% confidence interval (CI) 1.12–1.52), women <85 at follow-up had a 54% increased risk (RR 1.54, 95% CI 1.20–1.98), and men <85 had a 36% increased risk (RR 1.36, 95% CI 1.01–1.82). We found no associations in persons 85+. Current smokers had an increased risk for vascular dementia but not for Alzheimer’s dementia. Pack-years were not associated with increased dementia risk, and former smoking was only associated with vascular dementia in men.

Conclusions
Current smoking was associated with an increased risk of dementia. Among those 85+ at follow-up, being a smoker 20+ years earlier was not associated with an increased risk of dementia, probably because death was a competing risk. In former smokers, there were no significant associations with dementia. Our results add to the literature an optimism about the effects of changing smoking habits and may encourage smoking cessation.

Christian Myrstad, Marie Larssen, Bo Engdahl & Geir Selbæk

Abstarct:

The prevalence of Alzheimer’s disease neuropathological changes (ADNCs), the leading cause of cognitive impairment, remains uncertain. Recent blood-based biomarkers enable scalable assessment of ADNCs¹. Here we measured phosphorylated tau at threonine 217 in 11,486 plasma samples from a Norwegian population-based cohort of individuals over 57 years of age as a surrogate marker for ADNCs. The estimated prevalence of ADNCs increased with age, from less than 8% in people 58–69.9 years of age to 65.2% in those over 90 years of age. Among participants aged 70 years or older, 10% had preclinical Alzheimer’s disease, 10.4% had prodromal Alzheimer’s disease and 9.8% had Alzheimer’s disease dementia. Furthermore, among those 70 years of age or older, ADNCs were present in 60% of people with dementia, in 32.6% of those with mild cognitive impairment and in 23.5% of the cognitively unimpaired group. Our findings suggest a higher prevalence of Alzheimer’s disease dementia in older individuals and a lower prevalence of preclinical Alzheimer’s disease in younger groups than previously estimated.

Dag Aarsland, Anita Lenora Sunde, Diego A. Tovar-Rios, Antoine Leuzy, Tormod Fladby, Henrik Zetterberg, Kaj Blennow, Kübra Tan, Giovanni De Santis, Yara Yakoub, Burak Arslan, Hanna Huber, Ilaria Pola, Lana Grötschel, Guglielmo Di Molfetta, Håvard K. Skjellegrind, Geir Selbaek & Nicholas J. Ashton

ABSTRACT

Objectives:
The study aims to conduct a systematic review of peer-reviewed articles about psychosocial interventions to reduce the caregiver burden in family caregivers of people with dementia to explore the effectiveness and the type of intervention and methodology used.

Methods:
Five databases were searched (AgeLine, CINAHL, MEDLINE, PsycINFO, PubMed) for studies reporting on experimental research of psychosocial interventions for dementia-related caregiver burden. Data quality checks were completed for included papers.

Results:
Forty-three studies were included in the analysis; about half of them (n = 24) were randomized controlled trials. The types of interventions most often used were psychoeducation (n = 21) and multi-component interventions (n = 12). The caregiver burden was after the intervention successfully reduced in about half of the studies (n = 19). Additionally, 10 studies had success in reducing caregiving burden in one of several assessment measures used. The studies using psychoeducation (57%) and multi-component (58%) intervention approaches had the highest success rates.

Conclusion:
Health professionals should be encouraged to implement psychosocial interventions for caregivers of patients with dementia.

Hande Kirisik Surer, Nilufer Korkmaz Yaylagul & Anne-Sofie Helvik

Introduction: Frontotemporal symptoms are usually associated with frontotemporal dementia (FTD), but people with all forms of dementia may develop these symptoms as the dementia disease progresses. Knowledge about psychosocial interventions that meet the needs of people with FTD symptoms, and literature on the subject, is hard to find. The aim of the study was to describe current practice as it is experienced by healthcare experts in the clinical field in Norway.

Method: Three focus groups were conducted. Healthcare personnel with clinical experience in care and treatment to people with FTD and other dementia diseases with frontotemporal symptoms were eligible for inclusion. Qualitative directed content analysis with open coding focusing on both manifest and latent content was applied.

Results: Four categories were described: (1) Dilemmas of anosognosia, (2) establishment of a diagnosis, (3) establishment of post-diagnostic support at home, and (4) establishment of care in the nursing home.

Conclusion: People with FTD and other dementias with frontotemporal symptoms need rigid, easy-to-understand, predictable surroundings and healthcare personnel that are clear, friendly, and respectful in their communication. Post-diagnostic support provided in flexible systems ensuring smooth transitions between services and levels of care is required. To ensure quality of care, frontline healthcare staff should be able to recognize FTD symptoms. To achieve this, supervision and training are needed. More research about clinical care interventions and how to derive good nursing practice should be prioritized.

Marit Mjørud, Anne-Brita Knapskog, Marit Nåvik & Janne Røsvik

Abstract

Background
Infections may contribute to Alzheimer’s disease (AD) pathogenesis. Prior studies on the relationship between Helicobacter pylori (H. pylori) infection and AD or dementia have shown differing results.ObjectiveWe investigated whether H. pylori serology is associated with the risk of AD and dementia in the Trøndelag Health Study (HUNT).
Methods
The HUNT cohort study measured serum H. pylori antibody titers using the Pyloriset EIA-IgG test. 22 years after baseline serum sampling, cognitive assessments were conducted using standardized tests and proxy interviews. We performed logistic regression (n = 1364) adjusted for sex and age to estimate odds ratios for cognitive outcomes. Subgroup analyses were stratified by sex, age, Apolipoprotein E4 (APOE ε4) carrier status and high sensitivity serum C-reactive protein levels and sensitivity analyses further adjusted for lifestyle and co-morbidity risk factors. Cox regression models (n = 4689) were used to estimate hazard ratios for all-cause mortality.
Results
H. pylori titers were not associated with AD (OR 0.99 per 1 SD higher titer, 95% CI 0.82-1.20) or dementia (OR 0.98, 95% CI 0.84-1.15). There were no associations between H. pylori seropositivity (≥ 300 titers) and AD (OR 1.10, CI 0.75-1.63) or dementia (OR 0.96, CI 0.68-1.32). Stratifications by sex, age, CRP, or APOE ε4 genotype and adjusting for additional covariates showed no associations. All-cause mortality was higher with H. pylori positivity (HR 1.07, CI 1.03-1.11).
Conclusions
H. pylori was not associated with later AD or dementia in this study. The relationship between specific versus multi-pathogenic infection burden and neurodegenerative diseases warrants further clarification.

Pieta T Kelsey, Geir Selbæk, Hugo Lövheim, Bjørn Olav Åsvold, Kristian Hveem, Brooke N Wolford & Håvard K Skjellegrind

Abstract

Introduction: Efficient and cost-effective diagnostic tools for supporting dementia assessment are increasingly important. We aimed to evaluate whether providing neuroradiologists with volumetric data from an automatic MRI software, NeuroQuant, enhanced the diagnostic accuracy of their visual MRI assessment.

Methods: Two neuroradiologists assessed brain MRIs from 366 patients (mean age 67.5 years, SD 9.2, and 52% females) with subjective cognitive decline (SCD, n 79), mild cognitive impairment (MCI, n 86), or dementia (n 201). The MCI and dementia patients were further diagnosed according to an etiology of Alzheimer’s disease (AD, n 217) versus non-AD (n 70). In random order the neuroradiologists visually evaluated medial temporal lobe atrophy (MTA, scale 0-4) with and without having access to the NeuroQuant report of age and sex adjusted volumetric percentiles of the hippocampus. Receiver operating characteristics (ROCs) analyses were conducted to calculate the area under the curves (AUCs) for the visual MTA, the automated NeuroQuant percentile, and the combined NeuroQuant-assisted MTA in discriminating dementia from SCD and AD from non-AD.

Results: The AUC of the visual MTA for dementia versus SCD discrimination increased slightly but not significantly when the neuroradiologists were provided with NeuroQuant results (AUC 0.76-0.79, p 0.28). Yet, the isolated NeuroQuant evaluation reached the highest accuracy (AUC 0.85, p < 0.001), significantly better than the MTA assessment (p 0.002) and the NeuroQuant-assisted MTA (p 0.04). Only the isolated NeuroQuant assessment discriminated AD from non-AD (AUC 0.60, p 0.006).

Conclusion: On the basis of our findings, we suggest an increased use of clinically approved automatic volumetry methods in radiological departments.

Karin Persson, Hanneke F M Rhodius-Meester, Trine Holt Edwin, Anne-Brita Knapskog, Peter Bekkhus-Wetterberg, Geir Selbæk, Knut Engedal, Till Schellhorn

Abstract

Bernt Bratsberg, Jennifer R Harris, Vegard Skirbekk, Yaakov Stern, Asta Kristine Håberg, Geir Selbæk, Bjørn Heine Strand, Trine Holt Edwin

Abstract
Introduction: It is unclear how dementia affects loss in life expectancy (LE). In this registry-based study, we aimed to study sex differences in LE and loss in LE in dementia, mild cognitive impairment (MCI), and subjective cognitive decline (SCD).

Methods: A total of 16,358 patients diagnosed with dementia, MCI, or SCD from the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) during 2009-2022 were included and followed up for mortality. Sex differences in LE and loss in LE were predicted using flexible parametric survival models and sex-specific mortality in the general population as reference.

Results: Among dementia patients, women with dementia had the largest loss in LE: 17 years loss at 60 years; correspondingly, men lost 13.5 years. Similar patterns were observed for MCI and dementia subtypes.

Discussion: Women with dementia or MCI had a larger loss in LE compared to men with these diagnoses.

Highlights: Women with dementia had the largest loss in life expectancy compared to the general population.The excess female loss in life expectancy was also evident for all the dementia subtypes and for mild cognitive impairment.The loss in life expectancy was more pronounced in younger patients with dementia, with a loss of 17 years in women at 60 years of age. Men, in comparison, lost 13.5 years at the same age.Subjective cognitive decline was associated with a minor loss in life expectancy in both sexes.

Rachel Amland, Geir Selbæk, Anne Brækhus, Hanneke F M Rhodius-Meester, Bjørn H Strand