Abstract Objectives The aim of the present study was to describe the association between behavioral and psychological symptoms and psychotropic drug use among older Swedish nursing home residents with cognitive impairment. Methods Data was collected from a questionnaire survey which was sent out between 4 and 12 February 2019 within the Swedish National Inventory of Care and Health in Residential Aged Care (SWENIS) II. Sixty municipalities in Sweden were randomly selected and invited. Of these, 49 municipalities accepted the invitation. Six withdrew resulting in 43 participating municipalities and 187 nursing homes. The final study population comprised 1,541 participants, 65 years or older, with cognitive impairment. The Swedish Prescribed drug register was utilized to identify psychotropic drug use. Backward eliminating binary logistic regression analyses were conducted. Results At least one psychotropic drug was used of 80.8% of the study population, 20.5% used at least one antipsychotic drug, 32.0% used anxiolytic drugs, 21.3% used hypnotic and sedatives, 58.4% used antidepressants and 32.1% of the residents used antidementia drugs. Among residents with mild cognitive impairment, anxiolytics were significantly associated with anxiety. Also, anxiolytics and hypnotics and sedatives were significantly associated with sleep and nighttime behavior disorders. Antidepressants were significantly associated with depression/dysphoria. The same pattern was found among residents with moderate cognitive impairment. However, anxiolytics were also significantly associated with worsening depression/dysphoria. Hypnotics and sedatives were also associated with anxiety and hallucinations. Moreover, antipsychotic drug use was significantly associated with agitation/aggression and anxiety. Among residents with severe cognitive impairment, antipsychotics, anxiolytics and hypnotics and sedatives were significantly associated with aberrant motor behavior. Anxiolytics were also significantly associated with anxiety and apathy/indifference, and hypnotics and sedatives were significantly associated with agitation/aggression and depression/dysphoria. Conclusions Psychotropic drug use is remarkably high among Swedish nursing home residents but the prevalence of antidementia drugs is somewhat low. Associations found, call for further studies examining the treatment of behavioral and psychological symptoms (BPS) in this vulnerable group of people.

OBJECTIVES:Nursing homes in Sweden provide housing and care for people aged 65 years or older who require assistance with everyday activities. An increasing number of nursing home residents have cognitive and functional decline, which can result in additional time needed for care provision. This study aimed to explore changes in resource use and associated factors in Swedish nursing homes over a 5-year period. METHODS:This repeated cross-sectional study analyzed baseline (2013-2014) and follow-up (2018-2019) proxy-rated data from 4599 participants from the Swedish National Inventory of Care and Health in Residential Aged Care study. Resource use was measured using the Resource Use in Dementia scale. Descriptive statistics, t-tests, chi-square tests, and multiple linear regressions were performed. RESULTS:Total resource use increased from 7.15 h/day to 7.83 h/day between baseline and follow-up. The number of residents living in a dementia unit increased from 34.6% to 43%. Higher independence in activities of daily living was associated with lower total resource use at follow-up while living in a dementia unit was associated with higher total resource use. Higher total resource use was associated with seven neuropsychiatric symptoms. For residents living in a dementia unit, four neuropsychiatric symptoms were associated with higher total resource use. CONCLUSIONS:Resource use in Swedish nursing homes increased between baseline and follow-up. These results may inform future policy, financing, and implementation decisions to support resource utilization in nursing homes.

Background The introduction of anti-amyloid treatments (AAT) for Alzheimer's disease (AD) has put the cost-effectiveness into focus. Objective Estimate the potential cost-effectiveness of diagnostic pathways combined with AAT for early AD. Methods Diagnostic accuracy of blood-based (BBM) and cerebrospinal fluid (CSF) biomarkers was obtained from Norwegian memory clinics using positron emission tomography (PET) as reference standard. In a health-economic model, the cost-effectiveness of three diagnostic strategies was estimated relying either on BBM (p-tau 217), CSF (Aβ 42/40 ratio), and BBM with CSF confirmatory testing and compared with standard of care (SoC) and compared with CSF-AAT. The model consisted of a decision tree reflecting the diagnostic process and a subsequent Markov cohort model starting at mild cognitive impairment due to AD. All strategies except SoC were combined with AAT including costs of treatment (assumed €5000/year), infusions and monitoring. Results Compared with SoC all three strategies (CSF-AAT, BBM-AAT, and BBM-CSF-AAT) resulted in QALY gains at higher costs, with an incremental cost-effectiveness ratio (ICER) of 110k€, 141k€ and 110k€ respectively. Compared with CSF-AAT both BBM-AAT and BBM-CSF-AAT strategies resulted in QALYs lost at lower costs, with an ICER of 27k€ and 109k€ respectively. Results were particularly sensitive to the price of AAT and possible subcutaneous administration. Conclusions Compared with SoC all three strategies are potentially not cost-effective as they exceeded the Swedish maximum willingness to pay threshold of €94,800 per QALY gained. BBM-CSF-AAT versus CSF-AAT is potentially cost-effective if willing to accept its QALY loss. Discussions on budget impact on different payers are needed after introducing AAT.

Introduction Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe. Methods A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia. A mixed regression model was fitted to time spent on instrumental or basic activities of daily living using disease severity and demographic characteristics. Results Daily informal care time was 0.5 hours higher in moderate compared to mild and 1.3h higher in severe compared to mild cognitive impairment. Likewise, this was 1.2h and 2.7h for functional disability and 0.3h and 0.6h for behavioral symptoms in the same directions. Discussion Estimates can be used in both single- and multi-domain health-economic models for dementia in European settings.

Objectives: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD. Methods: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop. Results: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating-sum of boxes, clinical dementia rating-global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from 2US$66 897 to US$11 896. Conclusions: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models.

Background Blood biomarkers with prognostic accuracy for Alzheimer's disease (AD) are crucial for selecting at-risk individuals for interventions. Altered protein N-glycosylation has been implicated in several pathogenic pathways in AD and could be an early AD biomarker. Methods We developed a mass spectrometry-based method to simultaneously quantify 62 blood N-glycan structures in individuals with biological or clinical AD and matched controls. We analysed N-glycan levels in a Swedish discovery cohort (n = 40) and validated our results in a Norwegian cohort (n = 60). Individuals were grouped according to N-glycan levels using unsupervised hierarchical clustering. Difference in disease progression between groups were modelled using linear mixed-effects models. Findings A subgroup of individuals exhibited low blood N-glycosylation (32.4% of Swedish cohort, 37.9% of Norwegian cohort). In the Swedish cohort, low N-glycosylation was associated with AD and cognitive decline. In the Norwegian cohort, low blood N-glycosylation showed no correlation with amyloid/tau, but importantly, strongly predicted future cognitive decline. In total, fourteen N-glycan structures were significantly less abundant in the low N-glycosylation group compared to the rest of the individuals in both cohorts. Interpretation Reduced blood N-glycan levels predict cognitive decline independent of amyloid or tau status. Blood N-glycome profiling could be used to identify individuals at risk for AD dementia.

ABSTRACTObjectivesMarket access and reimbursement decisions for new Alzheimer’s disease (AD) treatments are informed by economic evaluations. An open-source model with intuitive structure for model cross-validation can support the transparency and credibility of such evaluations. We describe the new IPECAD open-source model framework (version 2) for the health-economic evaluation of early AD treatment and use it for cross-validation and addressing uncertainty.MethodsA cohort state transition model using a categorized composite domain (cognition and function) was developed by replicating an existing reference model and testing it for internal validity. Then, features of existing “ICER” and “AD-ACE” models assessing lecanemab treatment were implemented for model cross-validation. Additional uncertainty scenarios were performed on choice of efficacy outcome from trial, natural disease progression, treatment effect waning and stopping rules, and other methodological choices. The model is available open-source as R code, spreadsheet and web-based version viahttps://github.com/ronhandels/IPECAD.ResultsIn the IPECAD model incremental life years, QALY gains and cost savings were 21-31% smaller compared to the ICER model and 36-56% smaller compared to the AD-ACE model. IPECAD model results were particularly sensitive to assumptions on treatment effect waning and stopping rules and choice of efficacy outcome from trial.ConclusionsWe demonstrated the ability of a new IPECAD opens-source model framework for researchers and decision-makers to cross-validate other (HTA submission) models and perform additional uncertainty analyses, setting an example for open science in AD decision modeling and supporting important reimbursement decisions.

Background Sense of coherence (SOC) is a disposition to perceive things as comprehensible, manageable and meaningful. Lower SOC is associated with subjective burden and psychological morbidity in family caregivers, including in dementia. However, the evidence-base mainly comprises small-scale or cross-sectional studies. More should be known about SOC stability, causal relationships, and international contexts. We aimed to study longitudinal links between dementia caregivers' SOC, subjective burden, and anxiety and depression symptoms in a multinational sample. Methods We analyzed the EU-Actifcare cohort (451 dyads of community-dwelling people with mild-moderate dementia and their caregivers). Caregivers' assessments included: SOC scale, Relatives' Stress Scale, Hospital Anxiety and Depression Scale. A cross-lagged panel model was used to investigate associations between these measures at baseline, 6 and 12-month follow-ups, controlling for covariates. Results Caregivers' subjective burden, anxiety and depression symptoms increased over time, SOC remaining overall stable. Considering the first six-month follow-up, we found bidirectional relationships between SOC and subjective burden, and SOC and anxiety symptoms, while lower SOC predicted depression symptoms but not vice-versa. For the remaining follow-up period, both anxiety and depression symptoms predicted lower SOC but not vice versa. Limitations Convenience sampling precludes full generalizability. Conclusions This large longitudinal study shed more light on interplays between SOC, subjective burden and mental health outcomes in dementia caregivers. Findings were consistent with SOC potential protective role against burden and psychological morbidity. However, they also supported reverse causality regarding part of the associations. Caregivers' SOC levels may be directly influenced by subjective burden and psychological morbidity.

It is increasingly clear that aberrant N-glycosylation of proteins is an early pathogenic trigger in Alzheimer’s disease (AD). Thus, we hypothesized that determination of the blood N-glycome could reveal AD-specific glycomic patterns, especially in early stages of the disease. For N-glycan quantification in blood, we developed a method based on porous graphite carbon liquid chromatography coupled to tandem mass spectrometry (PGC-LC-MS/MS). We simultaneously determined levels of 62 N-glycan structures in 100 individuals from two different cohorts. In the Swedish National Study on Aging and Care in Nordanstig (SNAC-N) cohort, we analyzed blood samples from 40 age- and sex-matched AD and control individuals. In the Norwegian Dementia Disease Initiation (DDI) cohort, we analyzed blood samples from 60 individuals from A-T-, A+T-, and A+T+ biomarker groups, matched by age, sex, and education. In the Swedish SNAC-N discovery cohort, a specific blood signature of low levels of a group of N-glycans was associated with AD dementia, lower cognitive function, as well as higher levels of AD biomarkers such as blood pTau217. In the Norwegian DDI cohort, a similar low N-glycosylation blood signature was associated with APOE4 genotype and future cognitive decline, but not with A/T status. In short, low levels of 14 N-glycan structures were associated with poor cognitive outcome in both cohorts. Here, we provided an extensive characterization of the blood N-glycome in AD. We showed that the blood N-glycome could predict cognitive decline in an amyloid/tau independent manner. Blood N-glycomics should be further developed as a minimally invasive prognostic biomarker in early stages of dementia.

ObjectiveThe quality of the relationship between persons with dementia and family carers influences health and quality-of-life outcomes. Little is known regarding those at higher risk of experiencing a decline in relationship quality, who could potentially benefit the most from interventions. We aimed to identify these risk profiles and explore the underlying factors.MethodsWe applied a latent profile analysis to relationship quality data from a 1-year follow-up of 350 dyads of persons with dementia and their informal carers from the Actifcare cohort in eight European countries. Assessments included sociodemographic, clinical, functional, psychosocial and quality-of-life measures. Relationship quality was assessed with the Positive Affect Index. A discriminant analysis explored factors influencing the risk profiles.ResultsThere were two relationship quality profiles among persons with dementia (gradually decreasing, 74.0%; low but improving, 26%) and two among carers (steadily poor, 57.7%; consistently positive, 42.3%). The ‘gradually decreasing’ profile (persons with dementia) was related to their levels of dependence and unmet needs, along with carers’ social distress and negative feelings, lower baseline RQ and sense of coherence. The ‘steadily poor’ profile (carers) was influenced by their social distress and negative feelings, lower sense of coherence and perceived social support. These two predominant profiles showed significant decreases in quality-of-life over one year.ConclusionsSpecific profiles of persons with dementia and their carers are at risk of worse relationship quality trajectories. By considering modifiable related factors (e.g., carers’ stress), our findings can help develop tailored, effective interventions.

Abstract Background As global aging accelerates, routinely assessing the functional status and morbidity burden of older patients becomes paramount. The aim of this study is to assess the validity of the comprehensive clinical and functional Health Assessment Tool (HAT) based on four cohorts of older adults (60 + years) from the Swedish National study on Aging and Care (SNAC) spanning urban, suburban, and rural areas. Methods The HAT integrates five health indicators (gait speed, global cognition, number of chronic diseases, and basic and instrumental activities of daily living), providing an individual-level score between 0 and 10. The tool was constructed using nominal response models, first separately for each cohort and then in a harmonized dataset. Outcomes included all-cause mortality over a maximum follow-up of 16 years and unplanned hospital admissions over a maximum of 3 years of follow-up. The predictive capacity was assessed through the area under the curve (AUC) using logistic regressions. For time to death, Cox regressions were performed, and Harrell’s C-indices were reported. Results from the four cohorts were pooled using individual participant data meta-analysis and compared with those from the harmonized dataset. Results The HAT demonstrated high predictive capacity across all cohorts as well as in the harmonized dataset. In the harmonized dataset, the AUC was 0.84 (95% CI 0.81–0.87) for 1-year mortality, 0.81 (95% CI 0.80–0.83) for 3-year mortality, 0.80 (95% CI 0.79–0.82) for 5-year mortality, 0.69 (95% CI 0.67–0.70) for 1-year unplanned admissions, and 0.69 (95% CI 0.68–0.70) for 3-year unplanned admissions. The Harrell’s C for time-to-death throughout 16 years of follow-up was 0.75 (95% CI 0.74–0.75). Conclusions The HAT is a highly predictive, clinically intuitive, and externally valid instrument with potential for better addressing older adults’ health needs and optimizing risk stratification at the population level.

Objectives Chronic pain is highly prevalent in nursing home residents and often occurs with depression as well as cognitive impairment, which can severely influence and limit the expression of pain.Methods The present cross-sectional study aimed to estimate the prevalence of pain, depressive mood, and cognitive impairment in association with pharmacological treatment against pain and depressive symptoms among Swedish nursing home residents.Results We found an overall pain prevalence of 52.8%, a prevalence of 63.1% for being in a depressive mood, and a prevalence of cognitive impairment of 68.3%. Among individuals assessed to have depressive mood, 60.5% were also assessed to have pain. The prevalence of pharmacological treatment for pain was 77.5 and 54.1% for antidepressants. Prescription of pharmacological treatment against pain was associated with reports of currently having pain, and paracetamol was the most prescribed drug. A higher cognitive function was associated with more filled prescriptions of drugs for neuropathic pain, paracetamol, and nonsteroidal anti-inflammatory drugs (NSAIDs), which could indicate an undertreatment of pain in those cognitively impaired.Conclusion It is important to further explore the relationship between pain, depressive mood, and cognitive impairment in regard to pain management in nursing home residents.

Objectives Decision-analytic models assessing the value of emerging Alzheimer’s disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD. Methods A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop. Results Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (CDR-SB, CDR-global, MMSE, FAQ) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6-5.2 years for control strategy, and from 0.1-1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0-0.6 and incremental costs (excluding treatment costs) from -US$66,897 to US$11,896. Conclusions Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend 1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, 2) a standardized reporting table for model predictions, and 3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health economic models.

The aim of this study was to estimate the potential cost-effectiveness of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) program. A life-time Markov model with societal perspective, simulating a cohort of people at risk of dementia reflecting usual care and the FINGER program. Costs were 1,653,275 and 1,635,346 SEK and quality-adjusted life years (QALYs) were 8.636 and 8.679 for usual care and the FINGER program, respectively, resulting in savings of 16,928 SEK (2023 US$) and 0.043 QALY gains per person, supporting extended dominance for the FINGER program. A total of 1623 dementia cases were avoided with 0.17 fewer person-years living with dementia. The sensitivity analysis confirmed the conclusions in most scenarios. The model provides support that programs like FINGER have the potential to be cost-effective in preventing dementia. Results at the individual level are rather modest, but the societal benefits can be substantial because of the large potential target population.

A reported objective of Swedish sheltered housing is to postpone care needs and relocation. The aim of this study was to describe migration patterns and explore predictors of relocation to nursing homes and mortality, in a sample of residents in sheltered housing and aging in place. To explore longitudinal differences between groups, study data were combined with registry data. The results showed that a higher percentage of residents in sheltered housing had relocated to a nursing home and deceased over a three-year time period, compared to aging in place, implying further interventions may be required to promote health in sheltered housing.

In Sweden, sheltered housing is a housing model that provides accessible apartments with elevated social possibilities for older people. The environment within sheltered housing is expected to support resident health and reduce the need for care services. A previous study has shown that with increasing levels of depressive mood and decreasing levels of self-rated health and functional status, those residing in sheltered housing report higher levels of thriving compared to those ageing in place. Therefore, the aim of this study was to illuminate aspects of sheltered housing that are facilitators and/or barriers to thriving. Seven semi-structured group interviews in five different sheltered housing accommodations in Sweden were conducted between April 2019 and January 2020 (N = 38). The results, analysed using qualitative content analysis and presented in a model developed by Grol and Wensing, illuminate the four main categories of facilitators and barriers to thriving: individual factors, social context, environmental factors and organisational context. The results of this study show that the factors that influence experiences of thriving in sheltered housing are multifaceted and interconnected. Although the supportive environment provided in sheltered housing seems to contribute to thriving, the limited consideration towards the shifting health of residents is a barrier to thriving. The results of this study may assist in implementing tailored interventions to help support thriving on various levels.