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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., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: 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 International Pharmaco-Economic Collaboration on Alzheimer's Disease (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., Methods: A 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 Institute for Clinical and Economic Review (ICER) and Alzheimer's Disease Archimedes Condition-Event Simulator (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 via https://github.com/ronhandels/IPECAD., Results: In the IPECAD model incremental life-years, quality-adjusted life-years (QALY) gains and cost savings were 21% to 31% smaller compared with the ICER model and 36% to 56% smaller compared with 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., Conclusions: We demonstrated the ability of a new IPECAD open-source model framework for researchers and decision makers to cross-validate other (Health Technology Assessment submission) models and perform additional uncertainty analyses, setting an example for open science in AD decision modeling and supporting important reimbursement decisions., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The implementation of disease-modifying treatments for Alzheimer's Disease (AD) will require cost-effective diagnostic processes. As part of The Precision Medicine In AD consortium (PMI-AD) project, the aim is to analyze the baseline costs of diagnosing early AD at memory clinics in Norway, Slovenia, and the Netherlands., Methods: The costs of cognitive testing and a clinical examination, apolipoprotein E, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), positron emission tomography and blood-based biomarkers (BBM), which are used in different combinations in the three countries, were analyzed. Standardized unit costs, adjusted for GDP per capita and based on Swedish conditions were applied. The costs were expressed in euros (€) as of 2019. A diagnostic set comprising clinical examination, cognitive testing, MRI and CSF was defined as the gold standard, with MRI mainly used as an exclusion filter., Results: Cost data were available for 994 persons in Norway, 169 in Slovenia and 1015 in the Netherlands. The mean diagnostic costs were 1478 (95% confidence interval 1433-1523) € in Norway, 851 (731-970) € in Slovenia and 1184 (1135-1232) € in the Netherlands. Norway had the highest unit costs but also the greatest use of tests. With a uniform diagnostic test set applied, the diagnostic costs were 1264 (1238-1291) €, in Norway, 843 (771-914) € in Slovenia and 1184 (1156-1213) € in the Netherlands. There were no major cost differences between the final set of diagnoses., Conclusions: The total costs for setting a diagnosis of AD varied somewhat in the three countries, depending on unit costs and use of tests. These costs are relatively low in comparison to the societal costs of AD., (© 2024 The Author(s). International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

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., (© 2024. The Author(s).)

Background: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention., Methods: This open-label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55-75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12-18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed., Findings: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference -0·16, 95% CI -0·29 to -0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found., Interpretation: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up., Funding: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AW received research grants from EU IMI2 (MOPEAD), JPND (ADDITION, EURO-FINGER, PMI-AD), IHI (PROMINENT), and the Swedish VINNOVA program (PREDEM)(all paid to institution) and is licence holder of RUD-instrument (in part); outside the submitted work. RH received research grants from JPND, ZonMW, IMI, H2020 (paid to institution); received consulting fees from Lilly Nederland, iMTA, Biogen Nederlands, Biogen MA, Eisai (paid to institution); is a member of ISPOR special interest group open-source models, IPECAD modelling group and Alzheimer Europe Expert Advisory Panel (unpaid); outside the submitted work. SA received grants from EU (Institutional grant [Horizon 2020 Research and Innovation Programme agreement 779238]); Region Occitanie/Pyrénées-Méditerranée (1901175); the European Regional Development Fund (MP0022856); MSD Avenir Inspire Chairs of Excellence (Alzheimer Prevention in Occitania and Catalonia, EDENIS, KORIAN, Pfizer, and Pierre-Fabre); AXA Personal (current); Biogen Personal (2022); Roche Personal (2021); Leventis foundation (2022); ADI (2022); and has a leadership role in the French Alzheimer association (Scientific Committee); outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear., Methods: MIND-AD mini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale., Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (β Lifestyle×Time  = 1.11, P = 0.038; β Lifestyle+medical food×Time  = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions., Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial., Trial Registration: ClinicalTrials.gov NCT03249688., (© 2024. The Author(s).)

The development of disease-modifying therapies (DMTs) for Alzheimer's disease (AD) has progressed over the last decade, and the first-ever therapies with potential to slow the progression of disease are approved in the United States. AD DMTs could provide life-changing opportunities for people living with this disease, as well as for their caregivers. They could also ease some of the immense societal and economic burden of dementia. However, AD DMTs also come with major challenges due to the large unmet medical need, high prevalence of AD, new costs related to diagnosis, treatment and monitoring, and uncertainty in the therapies' actual clinical value. This perspective article discusses, from the broad perspective of various health systems and stakeholders, how we can overcome these challenges and improve society's readiness for AD DMTs. We propose that innovative payment models such as performance-based payments, in combination with learning healthcare systems, could be the way forward to enable timely patient access to treatments, improve accuracy of cost-effectiveness evaluations and overcome budgetary barriers. Other important considerations include the need for identification of key drivers of patient value, the relevance of different economic perspectives (i.e. healthcare vs. societal) and ethical questions in terms of treatment eligibility criteria., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Introduction: Inferring the timeline from mild cognitive impairment (MCI) to severe dementia is pivotal for patients, clinicians, and researchers. Literature is sparse and often contains few patients. We aim to determine the time spent in MCI, mild-, moderate-, severe dementia, and institutionalization until death., Methods: Multistate modeling with Cox regression was used to obtain the sojourn time. Covariates were age at baseline, sex, amyloid status, and Alzheimer's disease (AD) or other dementia diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Cohort and Memento)., Results: Using 80,543 patients, the sojourn time from clinically identified MCI to death across all patient groups ranged from 6.20 (95% confidence interval [CI]: 5.57-6.98) to 10.08 (8.94-12.18) years., Discussion: Generally, sojourn time was inversely associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

β-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer's disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinicians of the European Alzheimer's Disease Consortium (EADC) discuss the critical relevance of introducing these new treatments in clinical care now. Given the complexity of AD it is unlikely that molecular single-target treatments will achieve substantially larger effects than those seen with current β-amyloid-targeting antibodies. Larger effects will most likely only be achieved incrementally by continuous optimization of molecular approaches, patient selection and combinations therapies. To be successful in this regard, drug development must be informed by the use of innovative treatments in real world practice, because full understanding of all facets of novel treatments requires experience and data of real-world care beyond those of clinical trials. Regarding the antibodies under discussion we consider their effects meaningful and potential side effects manageable. We assume that the number of eventually treated patient will only be a fraction of all early AD patients due to narrow eligibility criteria and barriers of access. We strongly endorse the use of these new compound in clinical practice in selected patients with treatment documentation in registries. We understand this as a critical step in advancing the field of AD treatment, and in shaping the health care systems for the new area of molecular-targeted treatment of neurodegenerative diseases., Competing Interests: D. Aarsland reports personal fees for advice and lectures from Eisai, Biogen, Eli Lilly, EIP Pharma, Roche Diagnostics, Sanofi, and Heptares, and grants from Roche Diagnostics, Sanofi and Evonik. D. Angioni reports being an investigator in clinical trials sponsored by Alector, Alzheon, Biogen, Eisai, Genentech, Green Valley, Hoffmann-La Roche, Janssen, Medesis Pharma, Nestle, Novo Nordisk, Otsuka, Regenlife, Toulouse University Hospital, and UCB Pharma. No direct personal benefit. M. Balasa reports no conflict of interest. M. Boban reports no conflict of interest. K. Bennys reports grants form Alzheon Inc, Araclon Biotech S.L., Biogen, Eisai, Roche Genentech. No personal fees. M. Boada reports fees for advice from Grifols, Araclon, Biotech, Roche, Biogen, Lilly, Merck, Zambon, Novo Nordisk, Bioiberica, Eisai, Servier, and Schwabe Pharma; fees for lectures from Roche, Biogen, Grifols, Nutricia, Araclon Biotech, Servier, and Novo Nordisk. A. Chincarini reports no conflict of interest. S. Engelborghs reports fees from Eisai, icometrix, Novartis, Roche all paid to institution, and personal fees from Roche and Biogen. L. Exalto received personal fees from Julius Clinical and Brain Research Center. A. Felbecker reports personal fees for advisory boards and lectures from Eisai, Eli Lilly, Schwabe Pharma AG, Ompharma, Roche Pharma, Specialty care Therapiezentren AG, and grants from Fujirebio. K. Fliessbach reports no conflict of interest. G.B. Frisoni reports funding through the Private Foundation of Geneva University Hospitals from: A.P.R.A. – Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Ivan Pictet, Genève; Race Against Dementia Foundation, London, UK; Fondation Child Care, Genève; Fondation Edmond J. Safra, Genève; Fondation Minkoff, Genève; Fondazione Agusta, Lugano; McCall Macbain Foundation, Canada; Nicole et René Keller, Genève; Fondation AETAS, Genève. He has received funding through the University of Geneva or Geneva University Hospitals: for IISSs from ROCHE Pharmaceuticals OM Pharma EISAI Pharmaceuticals Biogen Pharmaceuticals and Novo Nordisk; for competitive research projects from: H2020, Innovative Medicines Initiative (IMI), IMI2, Swiss National Science Foundation, and VELUX Foundation as well as payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from: Biogen, Roche, Novo Nordisk, GE HealthCare, all through the institution. A.J. Garza-Martinez reports no conflict of interest. T. Grimmer reports consulting fees from AbbVie, Advantage Therapeutics Alector, Anavex, Biogen, BMS, Cogthera, Iqvia, Noselab, NuiCare, Orphanzyme Eisai, Eli Lilly, Functional Neuromodulation, Grifols, Janssen, Novo Nordisk, Roche Pharma, UCB, and Vivoryon, and lecture fees from Biogen, Eisai, Grifols, Medical Tribune, Schwabe, Synlab, Novo Nordisk, and Roche Pharma. Her served as Principal Investigator in drug trials by AbbVie, Advantage Therapeutics, Alector, Anavex, Biogen, Eli Lilly, Functional Neuromodulation, Roche Pharma, UCB, and Vivoryon; The Institution received payment for study performance. Further grants to his institution from: Biogen and Eisai and Roche Diagnostics. L. Froelich reports grants and personal fees for lectures and advice from Roche, and personal fees for lectures and advice from Eisai, Araclon/Grifols, Eli Lilly, Noselab, NovoNordisk, BioVie, Biogen, MerckSharpe and Dohme, Neurimmune, TauRX, Dr. Willmar Schwabe Otsuka/Avanir, Axon Neuroscience, Pharmatropix, Neuroscios, Vivoryon, Hummingbird, Anavex, and Boehringer Ingelheim. B. Hanseeuw reports personal fees for advice and lectures from Eisai, Roche, Biogen, and grants from Fonds National de la Recherche Scientifique, Fondation Stop Alzheimer, and WEL Research institute (WELBIO). J. Hort reports consulting and lecture fees from Schwabe, Eisai, and Eli Lilly and holds stock options in Alzheon. A. Ivanoiu reports no conflict of interest. F. Jessen has reports honoraria for advisory boards and presentations from Abbvie, AC immune, Biogen, Eli Lilly, Eisai, GE Healthcare, Grifols, Janssen-Cliag and Roche. L. Krajcovicova reports no conflict of interest. S. Klöppel reports fees for advice and lectures from Biogen, Eisai Switzerland, Lundbeck, and OM Pharma. M.G. Kramberger reports no conflict of interest. B. McGuinness reports personal fees from Eisai, Biogen, Eli Lilly, and Nutricia. P. Mecocci reports personal fees for advice and lectures from Lundbeck and Lilly, and non-financial support from Merck. A. de Mendonca reports no conflict of interest. A. Nous reports no conflict of interest. P.J. Dr. Ousset reports research grants from Acadia Pharmaceuticals, Alzheon Inc., Araclon Biotech S.L., AstraZeneca, Biogen, Avanir Pharmaceuticals, Eisai Inc., Eli Lilly, Genentech, Inc., Hoffmann-La Roche, Janssen Research and Development, Merck Sharp and Dohme, Novartis Pharmaceuticals, Shanghai Greenvalley Pharmaceutical Co., TauRx Therapeutics Ltd, UCB Biopharma without personal fee. He reports personal fees for advice from Lilly France. C. Paquet reports no conflict of interest. R. Perneczky reports personal fees for advice and lectures from Biogen, Eisai, Eli Lilly, Grifols, Novo Nordisk Roche, Schwabe, and GSK, and grants from Astra Zeneca, Roche, Janssen Cilag, Eli Lilly, and Takeda. O. Peters reports grants from Alector and Predemtec, grants and personal fees for advice and lectures from Biogen, Eisai, Roche, Noselab, and Novo Nordisk, personal fees for advice and lectures from Grifols, Lilly, Prinnovation, Medtrix, Neurolive, and Neurotransdata. F. Piazza reports consulting fees from Alector, Araclon, Alnylam, Biogen, Lilly, and Roche, and personal honoraria for advisory board membership from Roche, Araclon and Lilly. He holds a patent for the ultrasensitive quantification of anti-amyloid antibodies in human biological fluids. D. Platone reports no conflict of interest. M. Riverol reports personal fees for advice and lectures from Grifols, Nutricia and Esteve. A. Ruiz reports grants from the Instituto de Salud Carlos III (ISCIII), the European Comision-IMI program, the EU-JPND , VLAIO, Janssen, Grifols SA, Roche AG, and Araclon Biotech; and personal fees from Landstenier Genmed, Glenn Biggs Institute, UTHSA, Fundación ADEY, and Novo Nordisk. G. Sacco reports no conflict of interest. I. Santana reports grants from Biogen, and personal fees from Eisai. N. Scarmeas reports grants from NIH, and NovoNordisc. E. Solje reports personal fees from Novartis, Novo Nordisk, Eisai, and Roche and personal fees from Roche. E. Stefanova reports no conflict of interest. S. Sutovsky reports lecture fees from Eisai, Biogen, Schwabe and Krka. M. Tabuas-Pereira reports no conflict of interest. W. van der Flier reports grants from ZonMW, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences and Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer and Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. She holds the Pasman chair. She is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences and Health (PPP-allowance; #LSHM20106). She is recipient of TAP-dementia (www.tap-dementia.nl), receiving funding from ZonMw (#10510032120003). TAP-dementia receives co-financing from Avid Radiopharmaceuticals and Amprion. All funding is paid to her institution. She reports fees to the institution for lectures from Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), Novo Nordisk, Springer Healthcare, and European Brain Council. She consulted the Oxford Health Policy Forum CIC, Roche, Biogen MA Inc, and Eisai. All funding is paid to her institution. WF participated in advisory boards of Biogen MA Inc, Roche, and Eli Lilly. WF is member of the steering committee of EVOKE/EVOKE+ (NovoNordisk). All funding is paid to her institution. WF is member of the steering committee of PAVE, and Think Brain Health. WF was associate editor of Alzheimer, Research and Therapy in 2020/2021. WF is associate editor at Brain. T. Welsh is Research and Medical Director of The Research Institute for the Care of Older People (RICE), Bath, UK, which runs a mixture of commercial and non-commercial research activity. Commercial research projects run in the Institute have been funded by: Lilly, Roche, Biogen, Eisai, Janssen, AC Immune, Novo Nordisk, Pfizer, Elan, Immunobrain, Actinogen, and Julius Clinical. A. Wimo report to be the License holder (part) of RUD instrument. B. Winblad reports no conflict of interest.

Background: The emergence of disease-modifying Alzheimer's (AD) treatments provides new hope to patients and families but concerns have been raised about the preparedness of healthcare systems to provide timely access to such treatments because of a combination of a complex diagnostic process and a large prevalent pool., Objectives: We assess the preparedness of Sweden, a high-income country known for its dementia-friendly policies, to diagnose AD patients eligible for treatment within a six-month window, given current capacity for specialist evaluations and biomarker testing. We calculate the investment requirements for Sweden to achieve this target over a timeframe of 20 years., Design: Desk research to identify data for population, mortality, disease burden, cost of services and current capacity, expert consultation to inform assumptions about patient journey, and use of a Markov model to predict waiting times. The model simulates the patients' journey through different evaluation stages: initial evaluation by a primary care specialist, neurocognitive testing by an AD specialist, and confirmatory biomarker testing with PET scanning or cerebrospinal fluid (CSF) testing. The model assumes specialist appointments and PET scans are capacity constrained, and patients progress from cognitively normal to MCI and from MCI to dementia in the resulting waiting times., Measurements: Projected waiting times for diagnosis of eligibility for disease-modifying Alzheimer's treatment from 2023 to 2042 assuming current capacity, assuming 20% of Swedish residents aged 60 years and above would seek an evaluation for cognitive decline. Investments required to scale capacity up to reach target of providing diagnosis within six months on average., Results: Initial average waiting times for AD specialist appointments would be around 21 months in 2023 and remain around 55 months through 2042, as demand would continue to outstrip supply throughout the 20-year model horizon. Waiting times for biomarker testing would be stable at less than four weeks, as patients would be held up in the queue for their first specialist consultations, and use of CSF testing is widely accepted in Sweden. An additional 25% of AD specialists would have to be added above the current growth trend to reduce waiting times to less than 6 months at an average annual cost of approximately 805 million SEK. The increased cost of volume of biomarker testing would amount to about 106 million SEK per year., Conclusions: At current capacity, the Swedish healthcare system is unable to provide timely diagnosis of patients eligible for disease-modifying AD treatment. Although future diagnostic technologies, such as digital cognitive assessments and blood tests for the AD pathology, might decrease demand for capacity-constrained services, substantial investments will be required to meet a target of less than six months of waiting time for a diagnosis., Competing Interests: Soeren Mattke serves on the board of directors of Senscio Systems, Inc., and the scientific advisory board of AiCure Technologies, Alzpath and Boston Millennia Partners. He has received consulting fees from Biogen, C2N, Eisai, Novartis, and Roche/Genentech. Anders Gustavsson is co-founder and partner of Quantify Research AB, providing consultancy services to pharmaceutical companies and other private and public organizations and institutions. He indirectly owns shares in and serves on the board of Mindmore AB. Lena Jacobs an employee of at Quantify Research AB. Anders Wimo reports funding by VINNOVA program: PREDEM, EU project IMI2 program: MOPEAD, EU project H2020 program: PRODEMOS, EU-project IHI:PROMINENT, EU-projects JPND: EURO-FINGER, PMI-AD, ADDITION, and is a license holder of the RUD-instrument. Bengt Winblad has taken part in one Scientific Advisory Board meeting for BioArctic where the lecanemab data were discussed. Linus Jönsson has received research funding to his institution from VINNOVA, FORTE, IHI, Novo Nordisk, serves on an advisory board for Servier, and receives license fees for the RUD instrument. Sebastian Palmqvist has received research funding to his institution from ki elements / ADDF, and consultancy/speaker fees from Bioartic, Biogen, Lilly, and Roche. Silke Kern has served on advisory boards and/or as consultant for Geras Solutions and Biogen. Maria Eriksdotter has served as consultant for Biogen and Roche. Ingmar Skoog reports no conflicts.

Slovenia, situated in Central Europe with a population of 2.1 million, has an estimated 44,278 individuals with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's dementia, rendering them potential candidates for disease-modifying treatment (DMT), such as lecanemab. We identified 114 potential candidates whose real-life expenses for diagnostic process surmount to more than €80,000. Treating all potential candidates nationwide would amount to €1.06 billion, surpassing Slovenia's entire annual medication expenditure for 2022 (€743 million). The introduction of DMTs and the associated logistics, along with potential complications, will significantly change societal, professional, and patient approach to treatment of Alzheimer's disease.

Exercise and protein for function and self-confidence - The OPEN model for community care of older persons Experiences from the COVID-19 pandemic indicate the need to introduce care routines for health promotion among recipients of care for older persons. A treatment model with daily repeated sit-to-stand exercises in combination with oral protein supplements twice daily has been evaluated in community care for older persons in the Stockholm Region; the Older Person's Exercise and Nutrition (OPEN) Study. The 3-month controlled study included 102 residents. A substantial part of the residents were able to follow the intervention, and to maintain or improve their chair-rising capacity, while also increasing their weight and muscle mass. Interview studies showed that the participants found the OPEN concept was easy to adopt, gave increased self-confidence and an increased sense of hope. The staff perceived the intervention as a potentially positive concept. The OPEN model is a method that may contribute to a health-promoting way of working in the care of older persons.

Background: Health-related quality of life (HR-QoL) is an important outcome for patients and crucial for demonstrating the value of new treatments. Health utility estimates in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are limited, especially in biomarker-confirmed populations. Besides, little is known about the longitudinal HR-QoL trajectory. This study aims to provide health utility estimates for SCD and MCI and investigate the QoL trajectory along the disease continuum., Methods: Longitudinal data from 919 SCD and 1336 MCI patients from the MEMENTO cohort were included. SCD was defined as clinical dementia rating (CDR) = 0, and MCI as CDR = 0.5. HR-QoL was measured using the EQ-5D-3L patient-reported instrument. Linear mixed-effect models (LMM) were used to assess the longitudinal change in HR-QoL and identify predictors of these changes., Results: Baseline health utilities were 0.84 ± 0.16 and 0.81 ± 0.18, and visual analogue scale (VAS) were 75.8 ± 14.82 and 70.26 ± 15.77 in SCD and MCI. In amyloid-confirmed cases, health utilities were 0.85 ± 0.14 and 0.86 ± 0.12 in amyloid-negative and amyloid-positive SCD, and 0.83 ± 0.17 and 0.84 ± 0.16 in amyloid-negative and amyloid-positive MCI. LMM revealed an annual decline in health utility of - 0.015 (SE = 0.006) and - 0.09 (SE = 0.04) in moderate and severe dementia (P < 0.05). There was a negative association between clinical stage and VAS where individuals with MCI, mild, moderate, and severe dementia were on average 1.695 (SE = 0.274), 4.401 (SE = 0.676), 4.999 (SE = 0.8), and 15.386 (SE = 3.142) VAS points lower than individuals with SCD (P < 0.001). Older age, female sex, higher body mass index, diabetes, cardiovascular history, depression, and functional impairment were associated with poor HR-QoL. Amyloid positivity was associated with an annual decline of - 0.011 (SE = 0.004, P < 0.05) health utility over time., Conclusions: Health utility estimates from this study can be used in economic evaluations of interventions targeting SCD and MCI. Health utility declines over time in moderate and severe dementia, and VAS declines with advancing clinical stages. Amyloid-positive patients show a faster decline in health utility indicating the importance of considering biomarker status in HR-QoL assessments. Future research is needed to confirm the longitudinal relationship between amyloid status and HR-QoL and to examine the level at which depression and IADL contribute to HR-QoL decline in AD., (© 2023. The Author(s).)

Neurodegenerative diseases are one of the most important contributors to morbidity and mortality in the elderly. In Europe, over 14 million people are currently living with dementia, at a cost of over 400 billion EUR annually. Recent advances in diagnostics and approval for new pharmaceutical treatments for Alzheimer's disease (AD), the most common etiology of dementia, heralds the beginning of precision medicine in this field. However, their implementation will challenge an already over-burdened healthcare systems. There is a need for innovative digital solutions that can drive the related clinical pathways and optimize and personalize care delivery. Public-private partnerships are ideal vehicles to tackle these challenges. Here we describe the Innovative Health Initiative (IHI) public-private partnership project PROMINENT that has been initiated by connecting leading dementia researchers, medical professionals, dementia patients and their care partners with the latest innovative health technologies using a precision medicine based digital platform. The project builds upon the knowledge and already implemented digital tools from several collaborative initiatives that address new models for early detection, diagnosis, and monitoring of AD and other neurodegenerative disorders. The project aims to provide support to improvement efforts to each aspect of the care pathway including diagnosis, prognosis, treatment, and data collection for real world evidence and cost effectiveness studies. Ultimately the PROMINENT project is expected to lead to cost-effective care and improved health outcomes., Competing Interests: ME and SE were employed by BioArctic AB. JL and LT were employed by Combinostics Oy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tate, Suárez-Calvet, Ekelund, Eriksson, Eriksdotter, Van Der Flier, Georges, Kivipelto, Kramberger, Lindgren, López, Lötjönen, Persson, Pla, Solomon, Thurfjell, Wimo, Winblad and Jönsson.)

Introduction: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components., Methods: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs., Results: In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care., Discussion: The huge costs of dementia worldwide place enormous strains on care systems and families alike. Although most people with dementia live in low- and middle-income countries, highest total and per-person costs are seen in high-income countries., Highlights: Global economic costs of dementia were estimated to reach US $1313.4 in 2019. Sixty-one percent of people with dementia live in low-and middle-income countries, whereas 74% of the costs occur in high-income countries. The impact of informal care accounts for about 50% of the global costs. The development of a long-term care infrastructure is a great challenge for low-and middle-income countries. There is a great need for more cost studies, particularly in low- and middle-income countries. Discussions of a framework for global cost comparisons are needed., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Lecanemab, an anti-amyloid antibody with effects on biomarker and clinical endpoints in early Alzheimer's Disease (AD), was granted accelerated approval by the FDA in 2023 and regulatory review in Europe is ongoing. We estimate the population potentially eligible for treatment with lecanemab in the 27 EU countries to 5.4 million individuals. Treatment costs would exceed 133 billion EUR per year if the drug is priced similarly as in the United States, amounting to over half of the total pharmaceutical expenditures in the EU. This pricing would be unsustainable; the ability to pay for high-priced therapies varies substantially across countries. Pricing similarly to what has been announced for the United States may place the drug out of reach for patients in some European countries. Disparities in access to novel amyloid-targeting agents may further deepen the inequalities across Europe in health outcomes. As representatives of the European Alzheimer's Disease Consortium Executive Committee, we call for pricing policies that allow eligible patients across Europe to access important innovations, but also continued investments in research and development. Infrastructure to follow up the usage of new therapies in routine care and new payment models may be needed to address affordability and inequalities in patient access., Competing Interests: No specific funding was received for the preparation of this manuscript. Authors have completed separate CoI forms. The authors declare the following Conflicts of Interest: LJ received research grants (paid to institution) by Vinnova, FORTE and Novo Nordisk, license fees for the RUD instrument paid to European Health Economics, advisory board honorarium from Laboratoires Servier, travel support from BioArctic AB. AW received grants from Vinnova and EU (PREDEM, MOPEAD, PRODEMOS, EURO-FINGER, PROMINENT, PMI-AD, ADDITION, paid to institution), and is a license holder of the RUD instrument. Member of MSAP for ADI (un-paid). RH received research grants from JPND, ZonMW, IMI, H2020 (paid to institution), consulting fees from Lilly Nederland, iMTA, Biogen Nederlands, Biogen MA Inc, Eisai Inc (paid to institution), member of ISPOR modeling SIG and IPECAD modeling group (un-paid). MB is Member of the Advisory Boards Grifols, Roche, Lilly, Araclon Biotech, Merck, Zambon, Biogen, Novo- Nordisk, Bioiberica, Eisai, Servier, Schwabe Pharma. SE received research grants from Interreg Vlaanderen-Nederland, Research Foundation Flanders (FWO), VLAIO, GSKE/FMRE (paid to institution), consulting fees from Icometrix, Novartis, Eisai (paid to institution), personal consulting fees from Roche and Biogen, personal honoraria from Eisai, Roche, travel support to institution from Biogen, Patent EP3452830B1 (institution), member of SMB/SAB for EU-H2020 project RECAGE. VP of Belgian Dementia Council (unpaid). LF received grants from EU (RADAR-AD, RECAGE, FRAILBRAIN, paid to institution), personal consulting fees from Biogen, Eisai, Grifols, Hummingbird, Infecto-Pharm, Janssen-Cilag, MSD, Neurimmune, Functional Neuromodulation, Noselab, NovoNordisk, Roche, TauRX, Schwabe, lecture honoraria from Hoffmann-LaRoche and Schwabe, personal advisory board honorarium from Avanir/Otsuka, Pharmatropix, FZ Jülich, Charité Berlin, Neuroscios, reMYND, Vivoryon. FJ received personal consulting fees and lecture honoraria from Eisai, Biogen, Lilly, and personal honoraria for participation in advisory board from AC Immune. PJO received grants from Alector, Alzheon, Araclon Biotech, Biogen, Avanir Pharmaceuticals, Cortexyme, Eisai, Eli Lilly, Green Valley Pharmaceutical, Hoffman-La Roche, Janssen, Novartis Pharmaceuticals, NovoNordisk, TauRx, UCB Biopharma (paid to institution). NS received grants from EU (EPAD) and NovoNordisk (paid to institution). Personal fee as member of SAB from Albert Einstein College of Medicine – NIH funded. PJV received grants from EU (AMYPAD, RADAR-AD, EPND), Zon-MW, Biogen, Amyloid biomarker study (paid to institution), honoraria from workshop grant writing by Stiftung Synapsis, Alzheimer Forschung Schweiz. Patent holder (PCT/NL2020/050216) on AD subtypes (all paid to institution). GW received research grant from Danish Ministry of Health (paid to institution). BW received personal honorarium for a 2 h meeting with BioArctic, member of SMB for Alzinova, member of SAB for Resverlogix, stocks in AlzeCure pharma. GJ, PK, MK and AM declare no conflicts of interest., (© 2023 The Author(s).)

Introduction: The credibility of model-based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision-making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge., Methods: Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants. Model outcomes were summarized, and cross-comparisons were discussed during a structured workshop., Results: A broad concordance was established among participants. Mean 10-year restricted survival and time in MCI in the control group ranged across 10 MCI models from 6.7 to 9.5 years and 3.4 to 5.6 years, respectively; and across 4 mild dementia models from 5.4 to 7.9 years (survival) and 1.5 to 4.2 years (mild dementia)., Discussion: The model comparison increased our understanding of methods, data used, and disease progression. We established a collaboration framework to assess cost-effectiveness outcomes, an important step toward transparent and credible AD models., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: 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., Methods: A life-time Markov model with societal perspective, simulating a cohort of people at risk of dementia reflecting usual care and the FINGER program., Results: 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., Discussion: 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., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: The negative effects of informal caregiving are determined by the characteristics of the caregiver-care receiver dyad and the context of care. In this study, we aimed to identify which subgroups of older informal caregivers (1) experience the greatest subjective burden and (2) incur a faster decline in objective health status., Methods: From a total of 3363 older participants in the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), we identified 629 informal caregivers (19.2%, mean age 69.9 years). Limitations to life and perceived burden were self-reported, and objective health status was quantified using the comprehensive clinical and functional Health Assessment Tool (HAT) score (range: 0-10). Ordered logistic regressions and linear mixed models were used to estimate the associations between caregiving-related exposures and subjective outcomes (cross-sectionally) and objective health trajectories (over 12 years), respectively., Results: Having a dual role (providing and receiving care simultaneously), caring for a spouse, living in the same household as the care receiver and spending more hours on caregiving were associated with more limitations and burden. In addition, having a dual role (β=-0.12, 95% CI -0.23 to -0.02) and caring for a spouse (β=-0.08, 95% CI -0.14 to -0.02) were associated with a faster HAT score decline. Being female and having a poor social network were associated with an exacerbation of the health decline., Conclusions: Both the heterogeneity among caregivers and the related contextual factors should be accounted for by policymakers as well as in future research investigating the health impact of informal caregiving., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Dr. Wimo reports license holder of the RUD instrument. Dr. Jönsson reports grants from Novo Nordisk, outside the submitted work; In addition, Dr. Jönsson has a patent RUD instrument licensed to European Health Economics AB.

Purpose: Health-related quality of life (HRQoL) is an important patient-related outcome for the assessment of interventions and treatments in older people. Understanding underlying mechanisms for HRQoL is crucial for improving care, rehabilitation and symptom relief. This study examined the associations between HRQoL and frailty, sarcopenia, dependence of ADL, physical function and nutritional status in older nursing home (NH) residents., Patients and Methods: This is a cross-sectional study employing baseline data from the Older Person's Exercise and Nutrition (OPEN) study. Residents ≥75 years and able to stand up from seated position, residing in eight nursing homes in Sweden, were recruited. The EuroQoL 5-dimension Questionnaire (EQ-5D-5L, 0-1) was used to assess HRQoL. For exposure, the FRAIL and SARC-F questionnaires, Bergs Balance Scale, Functional Independence Measure (FIM), and Mini Nutritional Assessment-Short Form (MNA-SF) were used, including chair-stand test, walking speed and some biochemical markers. Descriptive and inferential statistics including linear regression models were applied., Results: Data from 113 residents (59% women, mean age 85 years) revealed a mean EQ-5D index of 0.76. After relevant adjustments, factors associated with low HRQoL were sarcopenia (p<0.001), cognitive function (p<0.001), dependence in ADL (p=0.002), low plasma-albumin (p=0.002) and impaired nutritional status (p=0.038)., Conclusion: This study displays evidence that modifiable conditions like sarcopenia and malnutrition are related to HRQoL in older NH residents. Such findings indicate a potential for physical exercise, including muscle training, and improved nutritional routines, including protein supplementation, to enhance nursing home care. Future studies, in larger NH populations, on exercise and nutrition for effects on HRQoL are needed., Competing Interests: AMB, GFI, EF, HG, ÅS, and SV declare no potential conflicts of interest in this study. TC has previously received unconditioned research funding as well as honoraria for lectures from the sponsoring agent (Nutricia) and personal fees from Abbott, Nestle, and Fresenius Kabi, outside the submitted work. AW reports personal fees from EISAI, outside the submitted work. In addition, AW has a patent RUD-instrument licensed to RUD-instrument., (© 2022 Boström et al.)

Objective: It has been found that COVID-19 increases deaths within common diseases in countries that have implemented strict lockdowns. In order to elucidate the proper national response to a pandemic, the mortality rates within COVID-19 and various diseases need to be studied in countries whose pandemic response differ. Sweden represents a country with lax pandemic restrictions, and we aimed to study the effects of COVID-19 on historical mortality rates within common diseases during 2020., Methods: Regression models and moving averages were used to predict expected premature mortality per the ICD-10 during 2020 using historical data sets. Predicted values were then compared to recorded premature mortality to identify changes in mortality trends., Results: Seasonal increased mortality was found within neurological diseases. Infectious diseases, tumours and cardiac disease mortality rates decreased compared to expected outcome., Conclusions: Changes in mortality trends were observed for several common diseases during the COVID-19 pandemic. Neurological and cardiac conditions, infections and tumours are examples of diseases that were heavily affected by the pandemic. The indirect effects of COVID-19 on certain patient populations should be considered when determining pandemic impact.

Introduction: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis., Methods: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC)., Results: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC)., Conclusion: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: The COVID-19 pandemic has caused large disruptions to healthcare systems. Refocus on COVID-19 related care might have contributed to indirect effects on other healthcare areas. Care focused on acute conditions have been negatively affected although research into the effects on chronic and care intensive patient groups such as patients with dementia diseases is lacking. In this study we evaluated dementia diagnosis trends in Sweden during 2015-2020 according to International Classification of Disease version 10 coding of common dementia diseases., Methods: Regional and national statistics in the form of International Classification of Disease version 10 coding, COVID-19 incidence, mortality data, and population census data were collected from the National Institute of Health and Welfare. Logistic regression analysis was performed to identify trends of dementia diagnosis during 2015-2020. Correlation test was performed between COVID-19 incidence, mortality rates, and dementia coding., Results: Dementia diagnosis incidence has been declining since 2015 and further decline was noted in many regions in Sweden during 2020. As COVID-19 incidence increased, fewer cases of dementia were diagnosed, a decrease that differentially impacted women and those who were advanced in age., Conclusions: Dementia diagnosis incidence in Sweden has been on a decline since 2015. The COVID-19 pandemic caused a further larger decline in dementia diagnosis incidence during 2020. COVID-19 incidence, but not mortality, was associated with decrease in dementia diagnosis incidence. There might be a large number of undiagnosed patients with dementia and healthcare reforms should be enacted to address this. Women and elderly are particularly vulnerable groups., (© 2022. The Author(s).)

Introduction: Dementias present a global health challenge and give rise to significant economic costs. This study aims to evaluate the economic impact of one-year outpatient healthcare, nursing home, and formal and informal home help costs for all patients referred to the Centre for Cognitive Impairments at the Department of Neurology, Ljubljana University Medical Centre, Slovenia., Methods: Data was acquired retrospectively from physicians' records and the costs for 2015 were calculated. Total costs were estimated by means of a bottom-up calculation of outpatient visits, diagnostic examinations and anti-dementia medication. In a subgroup of 120 patients with dementia, the Resource Utilization in Dementia questionnaire was used to estimate formal and informal care costs., Results: A total of 720 patients visited the memory clinic in 2015. Diagnosis at first visit was subjective cognitive or mild cognitive impairment (SCI/ MCI) for 322 patients, dementia for 258 patients, and psychiatric or other disorders for 140 patients. The average annual cost per patient was EUR 578. It was highest for patients with dementia (EUR 751), EUR 550 for patients with SCI/MCI, and lowest for patients with psychiatric and other disorders (EUR 324). Monthly informal and social care costs were between EUR 1,037 and EUR 3,369, depending on the methodology used., Conclusion: The cost of diagnosing a cognitive disorder depends on how extensive the diagnosis is. With an estimated prevalence of 34,137 persons with dementia in Slovenia, basic diagnostic investigations incur costs of approximately EUR 7 million. Direct medical costs represent a smaller portion of total dementia costs; this is because annual costs for formal and informal home help are estimated at EUR 265 million and nursing home placements at EUR 105 million., Competing Interests: Conflicts of interest The authors declare that no conflicts of interest exist., (© 2022 National Institute of Public Health, Slovenia, published by Sciendo.)

Background: The global burden of dementia is increasing. As diagnosis and treatment rates increase and populations grow and age, additional diagnosed cases will present a challenge to healthcare systems globally. Even modelled estimates of the current and future healthcare spending attributable to dementia are valuable for decision makers and advocates to prepare for growing demand., Methods: We modelled healthcare spending attributable to dementia from 2000 to 2019 and expected estimated future spending from 2020 to 2050 under multiple scenarios. Data were from the Global Burden of Diseases 2019 study and from two systematic literature reviews. We used meta-regression to estimate the fraction of dementia spending that is attributable to dementia for those receiving nursing home-based care and for those receiving community-based care. We used spatiotemporal Gaussian process regression to account for data missingness and model diagnosis and treatment rates, nursing home-based care and community-based care rates, and unit costs for the many countries without their own underlying estimates. Projections of future spending estimate a baseline scenario from 2020 to 2050 based on ongoing growth. Alternative scenarios assessed faster growth rates for dementia diagnosis and treatment rates, nursing home-based care, and healthcare costs. All spending is reported in 2019 United States dollars or 2019 purchasing-power parity-adjusted dollars., Findings: Based on observed and modelled inputs, we estimated that global spending on dementia increased by 4.5% (95% uncertainty interval: 3.4-5.4%) annually from 2000 to 2019, reaching $263 billion (95% uncertainty interval [UI] $199- $333) attributable to dementia in 2019. We estimated total healthcare spending on patients with dementia was $594 billion (95% UI $457-$843). Under the baseline scenario, we estimated that attributable dementia spending will reach $1.6 trillion (95% UI $0.9-$2.6) by 2050. We project it will represent 11% (95% UI 6-18%) of all expected health spending, although it could be as high as 17% (95% UI 10-26%) under alternative scenarios., Interpretation: Health systems will experience increases in the burden of dementia in the near future. These modelled direct cost estimates, built from a relatively small set of data and linear time trends, highlight the magnitude of health system resources expected to be used to provide care and ensure sufficient and adequate resources for aging populations and their caretakers. More data are needed to corroborate these important trends., Competing Interests: J L Dieleman reports support from Gates Ventures. A Wimo reports support from WHO, Merk, and Gates Ventures to his institution and private payments from RUD Instrument and Eisai, all outside submitted work. All other authors declare no competing interests., (© 2022 The Authors.)

Background: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear., Objectives: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD., Methods: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes., Results: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned., Conclusions: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions)., Competing Interests: Dr. Andrieu reports grants from EU – JPND program – MIND-AD project, during the conduct of the study; grants from EU – H2020 program – PRODEMOS project, grants from CNAV, personal fees and non-financial support from Nestlé SA, outside the submitted work. Dr. Broersen is employee of Danone Nutricia Research. Dr. Coley reports grants from Agence Nationale de la Recherche (ANR), during the conduct of the study. Dr. Wimo reports personal fees from Biogen, from Eisai, grants from Merck, outside the submitted work. Dr. Soininen reports grants from Academy of Finland for JNPD EU project, during the conduct of the study; personal fees from Consultation fee, outside the submitted work. Dr. Hartmann reports grants from BMBF-JPND, grants from EU FP7 LipiDiDiet, during the conduct of the study. Dr. Solomon reports grants from European Research Council grant 804371, grants from Alzheimerfonden, grants from Academy of Finland, during the conduct of the study. Dr. Kivipelto reports grants from The EU Joint Programme – Neurodegenerative Disease Research (JPND), Alzheimerfonden, Hjärnfonden, Center for Innovative Medicine (CIMED) at Karolinska Institutet South Campus, Knut and Alice Wallenberg Foundation, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Joint Program of Neurodegenerative Disorders – prevention (EURO-FINGERS), Region Stockholm (ALF, NSV), Stiftelsen Stockholms sjukhem, Swedish Research Council for Health Working Life and Welfare (FORTE), during the conduct of the study; and was an invited speaker and received an honorarium at an industry-led symposium including Biogen, Nutricia and Nestlé, outside the submitted work.

Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition., Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline., Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n = 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms., Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p &lt; 0.001) decrease in HRQoL utilities and a one-unit increase in depressive symptoms was associated with a -0.004 (p &lt; 0.001) decrease in HRQoL utilities., Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.

Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China. Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China. Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities. Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes., Competing Interests: AG and MM were employed by Philips VitalHealth. LS and XY were employed by Fuzhou Comvee Network &Technology Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hafdi, Eggink, Hoevenaar-Blom, Witvliet, Andrieu, Barnes, Brayne, Brooks, Coley, Georges, van der Groep, van Marwijk, van der Meijden, Song, Song, Wang, Wang, Wang, Wimo, Ye, van Charante and Richard.)

Objectives: Interindividual response variability to nutrition and exercise interventions is extensive in older adults. A group of nursing home (NH) residents participated in a combined intervention. The objective of this post-hoc analysis was to identify factors associated with intervention response measured by change in physical function and body composition., Design: Post-hoc analyses in the Older Person's Exercise and Nutrition study, a 2-arm randomized trial. The primary outcomes were 30-second Chair Stand Test and composite scores combining physical function and fat-free mass. A secondary outcome was intervention adherence. A 12-week intervention of sit-to-stand exercises and protein-rich nutritional supplements did not improve chair-stand capacity vs control on intention-to-treat basis., Setting and Participants: Residents ≥75 years of age from dementia and somatic units in eight NHs in Sweden., Methods: Logistic regressions were performed to define factors associated with response (maintenance/improvement) or nonresponse (deterioration) in 30-second Chair Stand Test, and with intervention adherence. Linear regressions were performed to explore factors associated with response in composite scores., Results: Mean age of participants (n = 52 intervention, n = 49 control) was 85.8 years. Sarcopenia was occurring in 74%. Sarcopenia at baseline (P = .005) and high adherence to nutritional supplements (P = .002) increased the odds of response. Higher independence in daily activities increased the odds of adherence to sit-to-stand exercises (P = .027) and the combined intervention (P = .020). Allocation to the intervention group and higher self-perceived health were associated with higher composite scores., Conclusions and Implications: NH residents with baseline sarcopenia, better self-perceived health, and high adherence to nutritional supplements benefitted most from a combined nutrition and exercise intervention regarding chair-stand capacity and composite scores of function and fat-free mass. Adherence was related to higher grade of independence. Understanding factors associated with response and adherence to an intervention will help target susceptible residents in most need of support and to optimize the outcome., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk., Methods and Analysis: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention., Ethics and Dissemination: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal., Trial Registration Number: ISRCTN15986016., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To investigate whether cholinesterase inhibitors (ChEIs) are associated with slower cognitive decline in Alzheimer dementia and decreased risk of severe dementia or death., Methods: Patients with Alzheimer dementia from the Swedish Dementia Registry starting on ChEIs within 3 months of the dementia diagnosis were included and compared to nontreated patients with Alzheimer dementia. In a propensity score-matched cohort, the association between ChEI use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores was examined with a mixed model, and severe dementia (MMSE score <10) or death as an outcome was assessed with Cox proportional hazards models., Results: The matched cohort included 11,652 ChEI users and 5,826 nonusers. During an average of 5 years of follow-up, 255 cases developed severe dementia, and 6,055 (35%) died. ChEI use was associated with higher MMSE score at each visit (0.13 MMSE points per year; 95% confidence interval [CI] 0.06-0.20). ChEI users had a 27% lower risk of death (0.73, 95% CI 0.69-0.77) compared with nonusers. Galantamine was associated with lower risk of death (0.71, 95% CI 0.65-0.76) and lower risk of severe dementia (0.69, 95% CI 0.47-1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07-0.28)., Conclusions: ChEIs are associated with cognitive benefits that are modest but persist over time and with reduced mortality risk, which could be explained partly by their cognitive effects. Galantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia., Classification of Evidence: This study provides Class III evidence that for patients with Alzheimer dementia ChEIs decrease long-term cognitive decline and risk of death and that galantamine decreases the risk of severe dementia., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer's Disease project, we assess GPs' attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis., Methods: Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries., Results: In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs' perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis., Discussion: Our findings provide insight into GPs' attitudes by exploring differences in perception and management of early diagnosis., Competing Interests: Laura Campo is a full‐time employee of Eli Lilly Italia S.p.A. and shareholder of Eli Lilly. Anders Wimo works as a consultant for Biogen and has received a research grant from MSD outside of this study. The other authors report no conflicts of interest regarding the publication of this article., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Purpose: Informal care constitutes an important part of the total care for people with dementia. Therefore, the impact of the syndrome on their caregivers as well as that of health and social care services for people with dementia should be considered. This study investigated the convergent and clinical validity of the CarerQol instrument, which measures and values the impact of providing informal care, in a multi-country sample of caregivers for people with dementia., Methods: Cross-sectional data from a sample of 451 respondents in eight European countries, collected by the Actifcare project, were evaluated. Convergent validity was analysed with Spearman's correlation coefficients and multivariate correlations between the CarerQol-7D utility score and dimension scores, and other similar quality of life measures such as CarerQol-VAS, ICECAP-O, and EQ-5D. Clinical validity was evaluated by bivariate and multivariate analyses of the degree to which the CarerQol instrument can differentiate between characteristics of caregivers, care receivers and caregiving situation. Country dummies were added to test CarerQol score differences between countries., Results: The mean CarerQol utility score was 77.6 and varied across countries from 74.3 (Italy) to 82.3 (Norway). The scores showed moderate to strong positive correlations with the CarerQol-VAS, ICECAP-O, and EQ-5D health problems score of the caregiver. Multivariate regression analysis showed that various characteristics of the caregiver, care receiver and caregiving situation were associated with caregiver outcomes, but there was no evidence of a country-level effect., Conclusion: This study demonstrates the convergent and clinical validity of the CarerQol instrument to evaluate the impact of providing informal care for people with dementia.

Background: For care planning and support, under-detection and late diagnosis of Alzheimer's disease (AD) is a great challenge. Models of Patient-Engagement for Alzheimer's Disease (MOPEAD) is an EU-funded project aiming at testing different strategies to improve this situation., Objective: To make a cost-consequence analysis of MOPEAD., Methods: Four screening strategies were tested in five countries (Germany, the Netherlands, Slovenia, Spain, and Sweden): 1) a web-approach; 2) Open-House initiative; 3) in primary care; and 4) by diabetes specialists. Persons-at-risk of AD in all strategies were offered referral to a hospital-based specialist. The primary health-economic outcome was the cost per true-positive case (TP) of AD from the screened population., Results: Of 2,847 screened persons, 1,121 screened positive (39%), 402 were evaluated at memory clinics (14%), and 236 got an AD diagnosis (8%). The cost per TP of those screened was €3,115 with the web-approach, €2,722 with the Open-House, €1,530 in primary care, and €1,190 by diabetes specialists. Sensitivity analyses that more likely reflect the real-world situation confirmed the results. The number-needed-to-screen was 30 with the web-approach, 8 with the Open-House and primary care, and 6 with the diabetes specialists.There were country differences in terms of screening rates, referrals to memory clinics, staff-types involved, and costs per TP., Conclusion: In primary care and by the diabetes specialist, the costs per TP/screened population were lowest, but the capacity of such settings to identify cases with AD-risk must be discussed. Hence new diagnostic strategies such as web-solutions and Open-House initiatives may be valuable after modifications.

Objectives: To study the prevalence and overlap between malnutrition, sarcopenia and frailty in a selected group of nursing home (NH) residents., Design: Cross-sectional descriptive study., Setting: Nursing homes (NH)., Participants: 92 residents taking part in an exercise and oral nutritional supplementation study; >75 years old, able to rise from a seated position, body mass index ≤30 kg/m2 and not receiving protein-rich oral nutritional supplements., Measurements: The MNA-SF and Global Leadership Initiative on Malnutrition (GLIM) criteria were used for screening and diagnosis of malnutrition (moderate or severe), respectively. Sarcopenia risk was assessed by the SARC-F Questionnaire (0-10p; ≥4=increased risk), and for diagnosis the European Working Group of Sarcopenia in Older People (EWGSOP2) criteria was used. To screen for frailty the FRAIL Questionnaire (0-5p; 1-2p indicating pre-frailty, and >3p indicating frailty), was employed., Results: Average age was 86 years; 62% were women. MNA-SF showed that 30 (33%) people were at risk or malnourished. The GLIM criteria verified malnutrition in 16 (17%) subjects. One third (n=33) was at risk for sarcopenia by SARC-F. Twenty-seven (29%) subjects displayed confirmed sarcopenic according to EWGSOP2. Around 50% (n=47) was assessed as pre-frail or frail. Six people (7%) suffered from all three conditions. Another five (5%) of the residents were simultaneously malnourished and sarcopenic, but not frail, while frailty coexisted with sarcopenia in 10% (n=9) of non-malnourished residents. Twenty-nine (32%) residents were neither malnourished, sarcopenic nor frail., Conclusions: In a group of selected NH residents a majority was either (pre)frail (51%), sarcopenic (29%) or malnourished (17%). There were considerable overlaps between the three conditions., Competing Interests: The authors have received grants from Gamla Tjänarinnor charitable fund, grants from Nutricia Global, during the conduct of the study.

Objectives: This exploratory study aimed at investigating profiles of care needs in people with mild to moderate dementia and examined variables associated with these profiles., Design: A longitudinal international cohort study., Setting and Participants: The baseline data of 447 community-dwelling dyads of people with dementia and their caregivers from the Access to Timely Formal Care (Actifcare) Study were included for analysis., Methods: A latent class analysis was applied to identify profiles of needs, measured with the Camberwell Assessment of Need for the Elderly as rated by the caregiver. We examined sociodemographic (eg, relative stress scale) and clinical characteristics (eg, neuropsychiatric inventory) associated with these profiles., Results: Four distinct need profiles were identified through latent class analysis. These comprised a "no need" profile (41% of the sample), a "met psychological needs" profile (25%), a "met social needs" profile (19%), and an "unmet social needs" profile (15%). A larger impact of caregiving on the caregiver's life as indicated by a higher relative stress scale score was associated with the "unmet social needs" profile., Conclusions and Implications: In this large European sample, there was a subgroup of persons with dementia with high "unmet social needs" whose caregivers simultaneously perceived high stress in their caregiving tasks. Identification of these profiles may help provision of appropriate support for these people., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Nursing home (NH) residents are often undernourished and physically inactive, which contributes to sarcopenia and frailty. The Older Person's Exercise and Nutrition Study aimed to investigate the effects of sit-to-stand exercises (STS) integrated into daily care, combined with a protein-rich oral nutritional supplement (ONS), on physical function, nutritional status, body composition, health-related quality of life, and resource use., Design: Residents in 8 NHs were randomized by NH units into an intervention group (IG) or a control group (CG) (n = 60/group). The IG was a combination of STS (4 times/day) and ONS (2 bottles/day providing 600 kcal and 36 g protein) for 12 weeks., Setting and Participants: The participants resided in NH units (dementia and somatic care), were ≥75 years of age, and able to rise from a seated position., Methods: The 30-second Chair Stand Test was the primary outcome. Secondary outcomes were balance, walking speed, dependence in activities of daily living, nutritional status and body composition, health-related quality of life, and resource use., Results: Altogether, 102 residents (age 86 ± 5 years, 62% female) completed the study. No improvement in the physical function assessments was observed in the IG, whereas body weight increased significantly (2.05 ± 3.5 kg, P = .013) vs the CG. Twenty-one (of 52) participants with high adherence to the intervention (ie, at least 40% compliance to the combined intervention) increased their fat free mass (2.12 kg (0.13, 4.26 interquartile range), P = .007 vs CG). Logistic regression analyses indicated that the odds ratio for maintained/improved 30-second Chair Stand Test was 3.5 (confidence interval 1.1, 10.9, P = .034) among the participants with high adherence compared with the CG., Conclusions/implications: Twelve-week intervention of daily STS combined with ONS in NH residents did not improve physical function, but increased body weight. Subgroup analyses indicated that high adherence to the combined intervention was associated with maintained or improved physical function and a gain of fat free mass., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hypertrophic cardiomyopathy is a heterogeneous disease in which an implantable cardioverter defibrillator (ICD) effectively prevents sudden cardiac death in at-risk individuals. Nevertheless, the cost-effectiveness of ICDs in this specific patient group has not been evaluated., Methods: A Markov cohort model was constructed to simulate the course of identified adult persons with hypertrophic cardiomyopathy with and without an ICD over the course of 12 years based on Swedish disease-specific unit costs. The age distribution was based on empirical data from the nationwide cohort of HCM patients with ICDs (mean age at the time of implant was 51.8 years). The outcomes were costs per saved life and cost per gained quality adjusted life year (QALY)., Results: Of 1000 simulated patients, 402 lives were saved after 12 years with an ICD at a cost of 646,000 Swedish krona (SEK), which corresponds to 57,118 Euro per saved life from the health care sector viewpoint. The cost per gained QALY (the incremental cost effectiveness ratio (ICER)) was 171,000 SEK (15,119 Euro). From a societal viewpoint, including effects on productivity losses, the use of an ICD was absolutely dominant (both cheaper and better, and thus an ICER is of no interest). Both the one-way sensitivity analyses and the probabilistic sensitivity analyses supported the findings in the base option., Conclusion: For identified patients with hypertrophic cardiomyopathy deemed at high risk of sudden cardiac death, the use of an ICD is extremely cost effective, both in terms of the cost for saved lives and gained QALY., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Loss to follow-up in dementia studies is common and related to cognition, which worsens over time. We aimed to (1) describe dropout and missing cognitive data in the Swedish dementia registry, SveDem; (2) identify factors associated with dropout; and (3) estimate propensity scores and use them to adjust for dropout., Methods: Longitudinal cognitive data were obtained from 53,880 persons from the SveDem national quality dementia registry. Inverse probability of censoring weights (IPCWs) were estimated using a logistic regression model on dropout., Results: The mean annualized rate of change in Mini-Mental State Examination (MMSE) in those with a low MMSE (0 to 10) was likely underestimated in the complete case analysis (+1.5 points/year) versus the IPCW analysis (-0.3 points/year)., Discussion: Handling dropout by IPCWs resulted in plausible estimates of cognitive decline. This method is likely of value to adjust for biased dropout in longitudinal cohorts of dementia., (© 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Aims: To explore to what extent type of residence (sheltered housing or ageing in place) contributes to thriving and well-being in older adults, when controlling for age, sex, living alone, being a widow and adjusting for functional status, self-rated health, and depressive mood., Design: A matched cohort study., Methods: A self-report survey was sent out to a total population of residents in all sheltered housings in Sweden and a matched control group ageing in place (N = 3,805). The data collection took place between October 2016-January 2017., Results: The interaction analyses related to thriving showed that with increasing level of depressive mood and decreasing levels of self-rated health and functional status, those residing in sheltered housing generally reported higher levels of thriving, as compared with those ageing in place. Well-being was not found to be significantly associated with type of accommodation., Conclusion: There may be features in sheltered housing that are associated with resident thriving especially among individuals with impairments of function, health or mood, although further studies are required to identify these specific features., Impact: This study informs staff and policymakers about thriving and well-being in sheltered housing accommodations. These findings may be used to further the development of sheltered housing accommodations., (© 2019 John Wiley & Sons Ltd.)

Objectives: Previously developed dementia caregiver profiles defined by caregiver age and burden, have been associated with caregiver quality of life, depression and perseverance time. The current aim was to investigate whether these caregiver profiles could predict subsequent service use. In addition, non-personal (e.g. meals on wheels) and supportive services (e.g. Alzheimer café) in early dementia were investigated as predictors. Methods: A total of 451 dyads of people with dementia and their informal caregivers from eight European countries were followed for one year. People were included if they did not use formal (personal) care but were expected to do so within 1 year. Logistic regression analyses were used with four clusters of service use as dependent variables (home social care, home personal care, day care and admission). The independent variables were caregiver profiles, and non-personal and supportive services at baseline. Results: Caregiver profiles were significant predictors of service use; those experiencing high strain were more likely to use formal care. The use of low-intensity, less intrusive services at baseline significantly predicted the use of home personal care and admission at follow-up. The use of day care at follow-up was predicted by the baseline use of supportive services. Conclusion: Caregiver profiles are valuable predictors for service use: this knowledge can aid professionals in ensuring optimal access to services, which is important for maintaining independence at home. In addition, the use of supportive and less intrusive, non-personal services in the early stages of dementia is to be advised.

Objective: To identify, in caregivers of patients with Alzheimer's disease (AD) dementia, factors associated with subjective (personal, physical, emotional, and social) and objective (informal caregiver time and costs) caregiver burden., Design: Prospective longitudinal European observational study: post-hoc analysis., Setting: Clinic., Participants: Community-dwelling patients in France and Germany aged ≥ 55 years (n = 969) with probable AD and their informal caregivers., Measurements: Mini-Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), 12-item Neuropsychiatric Inventory (NPI-12), Zarit Burden Interview (ZBI), informal caregiver basic and instrumental ADL hours (Resource Utilization in Dementia instrument), and informal caregiver costs. Mixed-effect models of repeated measures (MMRM) were run, including baseline and time-dependent covariates (change from baseline [CFB] to 18 months in MMSE, ADCS-ADL, and NPI-12 scores) associated with CFB in ZBI score/informal caregiver time over 36 months (analyzed using linear regression models) and informal caregiver costs over 36 months (analyzed using generalized linear models)., Results: Greater decline in patient function (ADCS-ADL) over 18 months was associated with increased subjective caregiver burden (ZBI), hours, and costs over 36 months. Increased behavioral problems (NPI-12) over 18 months also negatively impacted ZBI. Cognitive decline (MMSE) over 18 months did not affect change in caregiver burden., Conclusions: Long-term informal caregiver burden was driven by worsening functional abilities and behavioral symptoms but not cognitive decline, over 18 months in community-dwelling patients with AD dementia. Identifying the drivers of caregiver burden could highlight areas in which interventions may benefit both caregivers and patients.