The Lancet Healthy Longevity

BackgroundDisease-modifying therapies (DMTs) for Alzheimers disease, including lecanemab and donanemab, have received regulatory approval in multiple jurisdictions. These therapies require complex diagnostic workup and safety monitoring, raising significant budget impact concerns for healthcare payers. No budget impact analysis specific to Ireland or comparable small European healthcare systems has been published. ObjectiveTo estimate the 5-year budget impact of introducing DMTs for early-stage Alzheimers disease in Ireland from the Health Service Executive (HSE) payer perspective. MethodsA budget impact model was developed following International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. The model incorporated Irish epidemiological data, published drug prices, and healthcare resource utilisation estimates. Three treatment uptake scenarios (conservative, base case, optimistic) were modelled over a 5-year time horizon. Sensitivity analyses examined parameter uncertainty. ResultsFrom an estimated eligible population of 11,568 individuals with early-stage Alzheimers disease, annual budget impact in Year 5 ranged from {euro}12.8 million (conservative: 3% uptake) to {euro}89.6 million (optimistic: 20% uptake), with a base case estimate of {euro}35.8 million (8% uptake). Cumulative 5-year budget impact ranged from {euro}32.0 million to {euro}224.0 million. Drug acquisition costs represented 61% of total expenditure, with diagnostic and monitoring costs comprising 24% and 15%, respectively. Sensitivity analysis identified drug price, eligible population size, and treatment uptake as the most influential parameters. ConclusionsIntroduction of DMTs for Alzheimers disease will have a substantial but manageable budget impact on the Irish healthcare system, contingent on treatment uptake rates constrained by diagnostic capacity. Strategic investment in diagnostic infrastructure, phased implementation, and negotiated drug pricing could mitigate budgetary pressures while enabling patient access to these novel therapies. Key Points for Decision MakersO_LIThis is the first budget impact analysis of disease-modifying therapies (DMTs) for Alzheimers disease specific to Ireland, a small European healthcare system with constrained diagnostic capacity. C_LIO_LIAnnual budget impact ranges from {euro}12.8 million (conservative scenario) to {euro}89.6 million (optimistic scenario) in Year 5, representing 0.05% to 0.33% of the total Health Service Executive budget. C_LIO_LIDrug acquisition costs account for 58-65% of total expenditure, with diagnostic workup and safety monitoring comprising substantial ancillary costs. C_LIO_LIPhased implementation aligned with diagnostic infrastructure expansion could enable budget-neutral introduction through efficiency gains in dementia care pathways. C_LI

BackgroundDementia diagnoses are captured across multiple routine data sources, but discrepancies between these may affect care and research. This study determined the prevalence and overlap of recorded dementia across primary care, hospital, and community prescribing data sources in a UK regional cohort, and examined whether outcomes differed by the setting in which dementia was first recorded. MethodsRetrospective cohort study of adults [&ge;]65 years (n=133,407) in a large Scottish health board. Dementia diagnoses recorded from 01/04/2016 to 01/04/2020 were identified across linked primary care, hospital discharge, and prescribing records. Associations between source of first recorded dementia diagnosis and subsequent mortality and emergency hospitalisation were estimated using Cox proportional hazards and Fine-Gray competing risks models. ResultsAt baseline (01/04/2016), 7544/133407 individuals (5.7%) had recorded dementia: 95.1% in primary care, 73.3% in hospital, and 54.3% in prescribing records. Over four years, 7359 of the remaining 125,863 individuals (5.8%) had newly recorded dementia: 70.2% in primary care, 22.2% in hospital, and 7.6% in prescribing records. Only 35.9% of hospital-recorded diagnoses were coded in primary care records within a year. People first diagnosed in hospital were older, more frail, more socioeconomically deprived, and had higher mortality than those first diagnosed in primary care (<30days: adjusted Hazard Ratio (aHR) 8.96, 95%CI 6.94-13.52; >365days: aHR 1.29, 95%CI 1.19-1.41). ConclusionsDementia is variably recorded across routine datasets, and the setting in which dementia is first recorded identifies groups with markedly different prognosis. Improved data source integration and scrutiny of hospital-based diagnostic pathways are needed to ensure diagnoses are reliably transferred and people with dementia receive timely, equitable post-diagnostic care.

BackgroundAntidepressant use is common in people with dementia. Antidepressants may be started to manage symptoms of dementia, rather than depressive and anxiety disorders. We hypothesised people prescribed antidepressants around the time of dementia diagnosis may have different characteristics from those with longstanding prescriptions. MethodsWe used linked primary care (Lambeth DataNet) and specialist (Clinical Record Interactive Search) data for patients with dementia in south London, UK. Antidepressant prescription was ascertained, and a new start was within one year before or after dementia diagnosis. Coded fields, a rating scale for neuropsychiatric symptoms and natural language processing of full-text were used to describe depression and anxiety. ResultsOf 3,713 patients with dementia, 28% were prescribed antidepressants within the year of dementia diagnosis, and 42% of these were new start prescriptions. Compared to the no antidepressant group, the new start group were more likely to be female, have vascular dementia and neuropsychiatric symptoms. Compared to the long-standing group, new start had fewer comorbidities; people from non-White ethnicities were more likely to lack documentation of depression or anxiety. Deprescribing was equally unlikely in new and long-term prescriptions (6.3% vs 5.5% per year of follow-up). ConclusionsThe high incidence of new prescribing, as well as the lack of deprescribing, points to unmet needs and a role for more proactive medication review. Further studies should include the clinician and patient voices to further understand how to improve non-pharmacological support for people at the threshold of dementia.

BackgroundGastrointestinal infections are a substantial public health issue in England. Local authority environmental and regulatory (ER) services support the prevention and control of gastrointestinal infections with food safety and infection control functions. However, there have been significant and inequitable cuts to local authority budgets, with ER services seeing expenditure reduced by 2.4% per capita in the most deprived compared to 1.2% per capita in the least deprived authorities. It is therefore imperative to understand the impact local funding cuts to ER services may have on gastrointestinal infection outcomes. MethodsWe use longitudinal data in England, at local authority district level, between 2010 and 2019. Exposures of interest were ER spending lines of food safety expenditure, and aggregated spending lines of food safety and infection control (FSIC) expenditure, and the number of food hygiene full time equivalent staff (FTE) per 10,000 of the population. Primary outcomes of interest were the number of laboratory-confirmed Campylobacter, Salmonella, and E. coli O157 infections, emergency hospitalisations due to GI infection, and the number of calls to NHS 111, all at the local authority level. We use fixed effects negative binomial modelling to estimate the association between relative change in the incidence rate of gastrointestinal infection outcomes and increases in each of our exposures. NHS 111 and hospital admission data were desegregated by age group, and age-exposure interactions were used to understand differential effects. This was not possible for pathogen data due to the small number of observations per year by species. ResultsNo significant relationship was found between expenditure or staff and foodborne pathogen incidence overall. When considered as a whole, we find no significant relationship between expenditure or staff levels and the number of hospital admissions for all age groups. However, when disaggregated by age, an increase of {pound}1 per capita in food safety expenditure was associated with a 1.34 % decrease in the rate of hospitalisations among 20-59-year-olds (IRR = 0.9866: 0.9738, 0.9996). In addition, an increase in food hygiene staffing per 10,000 of the population was associated with a 36% decrease in the rate of hospitalisations in 60-64-year-olds (IRR =0.64: 0.48 0.86). Results also identified an increase in resource allocation was associated with increased rate in hospital admissions for some age groups. A {pound}1 per capita increase in food safety expenditure was associated with a 3% increase in hospitalisations for 5-9 (IRR=1.0300: 1.0001, 1.0607) and a 2.3 % increase for 10-19-year-olds (IRR=1.023:1.004,1.043). {pound}1 per capita increase in FSIC expenditure was associated with a 1% increase in admissions for 75+ (IRR=1.009:1.001,1.018). Finally, a one unit increase in staff per 10,000 of the population was associated with a 134% increase admission for 5-9-year-olds (IRR =2.34:1.60, 3.43) and 50% increase amongst 10-19-year-olds (IRR=1.50:1.14, 1.98), whilst no significant relationship was identified between the number of NHS 111 calls and exposures of interest. DiscussionOverall, no significant relationship was identified between expenditure or staff levels on the number of laboratory confirmed pathogens, hospital admissions or NHS 111 calls. However, age-specific patterns suggest an increased resource allocation may be protective for some groups in preventing hospital admissions. While increased rates of illness for children and 75+ years may reflect differences in exposure, detection or healthcare seeking behaviour or other unknown factors. Building on previous research evidencing the inequal reductions in service expenditure, and the impacts on service capacity, these results highlight the potential role of local funding cuts on GI infection health outcomes. Further research is warranted to understand the mechanisms driving different effects and to understand how service provision interacts with sociodemographic factors.

This study challenges the assumption that undiagnosed cognitive impairment (CI) is driven primarily by patient-level barriers like poor awareness. In a population-weighted cohort of 1,856 older Singaporeans, CI prevalence was 24.7% (95%CI 18.8-31.8); yet the undiagnosed rate was high (81.4%, 95%CI 65.6-90.9), especially for mild CI (97.9%, 95%CI 94.1-99.3). This diagnostic gap persisted despite high symptom awareness (81.3%, 95%CI 63.6-91.5) and help-seeking intent (63.3%, 95%CI 47.5-76.7), with informants becoming key as CI worsened. Findings suggest successful public health campaigns have shifted the bottleneck from community awareness to healthcare system capacity, creating an opportunity for a policy shift to meet rising demand for diagnosis--by empowering primary care with efficient case-finding tools, formalizing integrated diagnostic pathways, and establishing channels for family informants involvement. From these findings, we conceptualized a paradox of success model, providing a framework for other health systems to adapt policy as public engagement grows.

ObjectivesTo characterize contemporary pharmacologic treatment patterns for Alzheimers disease and related dementias (ADRD) among U.S. long-term care residents and to examine facility- and resident-level factors associated with treatment. DesignRetrospective, observational study. Setting and ParticipantsElectronic health record data from 1,675,873 long-term care residents in the PointClickCare Life Sciences database included 359,801 with a documented ADRD diagnosis in skilled nursing facilities in the U.S. (January-April 2025). MethodsResidents were classified as treated/untreated based on receipt of guideline-directed ADRD therapy, consistent with Alzheimers Association guidelines. Analyses incorporated demographics, comorbidities, medication burden, and facility characteristics. Multivariate logistic regression estimated odds of receiving guideline-concordant therapy. ResultsOverall, 72.5% of residents with ADRD received [&ge;]1 pharmacologic treatment recommended for ADRD. Treatment was most common among residents with Lewy body dementia (83.9%) and early-onset Alzheimers disease (82.3%) and least frequent among residents aged [&ge;]90 years (65.1%), Black/African American residents (66.8%), and those with cerebral degeneration (66.8%). Treated residents exhibited higher medication burden (mean 4.4 vs 3.3). Diagnoses for other chronic conditions as well as specific ADRD subtypes strongly impacted probability of treatment; diabetes and hyperlipidemia were associated with lower odds of treatment, whereas ADRD subtypes strongly predicted treatment. Conclusions and ImplicationsMore than one-quarter of residents with ADRD remain untreated with guideline-recommended pharmacotherapy, and treatment varied significantly by non-clinical predictors. These findings underscore the need to investigate and understand possible treatment disparities, optimize polypharmacy management, and discover new ADRD treatments, as current options are often ineffective with many side effects. Brief SummaryThis study used real-world data from electronic health records (EHR) to understand treatment patterns of those with Alzheimers disease and related dementias (ADRD) in U.S. long-term care facilities. International Classification of Diseases Tenth Revision, Clinical Modification (ICD-10) codes were used to identify ADRD diagnoses and medication orders were used to identify treatment. From January to April 2025, there were 359,801 with a documented ADRD diagnosis in skilled nursing facilities. Over 25% of those with ADRD did not have a medication order for a guideline-recommended pharmacological treatment. Comorbidities of diabetes and hyperlipidemia were associated with lower odds of receiving ADRD treatment, suggesting concerns related to adverse drug reactions and competing clinical priorities. The use of cognitive and disease-modifying therapies was low compared to behavioral/psychiatric medications; this finding suggests a need for more effective and safe drugs that target the root causes of ADRD opposed to the behavioral and psychiatric complications. Taken together, the results of this study call for targeted interventions to address disparities in treatment, enhanced clinical decision-making support regarding polypharmacy, and improved pharmacological options for those with ADRD.

BackgroundThis study used qualitative methods to test and refine a framework for educating cognitively unimpaired individuals about their individual risk for Alzheimers disease and related dementias (ADRD) and intrapersonal health belief factors as part of the TEACH (Tailored Education for Aging and Cognitive Health) intervention. MethodWe assessed individuals ADRD risk factors and health belief concepts. Personalized data were presented individually, followed by a semi-structured phenomenographic interview. Applied thematic analysis was used to identify representative statements, trends, and differences. ResultsIn N=11 individual interviews with middle-aged and older participants (ages 49-69; 45% women), participants had generally positive experiences of learning their personal dementia risk; the information was perceived to be unsurprising and occasionally consoling. They demonstrated a good understanding of the health belief concepts, including identifying relationships between intrapersonal health beliefs and health behaviors. Participants provided feedback on the visual aids and methods of conveying health belief information. ConclusionsWe used qualitative data from individual interviews to refine an explanatory framework for educating individuals about their personalized risk for ADRD and intrapersonal health beliefs that may be barriers or facilitators of health behavior change. The refined TEACH intervention is designed to promote long-term maintenance of target health behaviors in middle-aged adults to mitigate ADRD risk.

ObjectiveIn England, since 2022, large businesses providing food in the out-of-home sector are required to display calorie information for non-prepacked food and non-alcoholic drink items. This study estimates long-term cost-effectiveness of the policy by extrapolating real-world evidence on short-term policy effects in England. DesignThe lifetime health economic impacts of calorie labelling were simulated using a microsimulation model. The analysis adopted a health systems perspective to compare the policy with a counterfactual no intervention scenario. The policy may impact calories consumed through consumer behaviour changes and through menu changes based on observations from real-world evaluations. Estimated changes to daily calorie intake are translated to weight changes. Simulated outcomes include changes in obesity, diabetes cases, cardiovascular events, quality adjusted life years (QALYs) and National Health Service costs with probabilistic sensitivity analysis to describe uncertainty. SettingA synthetic population for England aged 13-79 combining data was generated the National Diet and Nutrition Survey (2009-19) and Health Survey for England (2018, 2019). ParticipantsNone ResultsThe policy is estimated to generate lifetime cost savings were estimated to be-{pound}9.15 (95% CI - {pound}31.63, {pound}2.50), and incremental QALYs 0.0021 (95% CI-0.0008, 0.0048) per person. The incremental net benefit at {pound}20,000 per QALY was {pound}50.23 (95% CI-{pound}16.41, {pound}74.68). Greater cost-savings and QALY gains were observed in the most deprived groups. DiscussionThe out-of-home calorie labelling policy in England is uncertain but most likely cost-effective with cost-savings and marginally beneficial to health. The results are driven by expected menu changes.

BackgroundTransthyretin amyloidosis cardiomyopathy (ATTR-CM) and Alzheimers disease (AD) are age-related disorders characterized by pathological protein aggregation. Despite shared risk factors and mechanisms, the relationship between ATTR-CM and AD remains poorly understood. MethodsWe performed a population-based case-control study using the French National Health Data System from 2019 to 2023. Individuals aged 65 years or older diagnosed with ATTR-CM were matched with controls without ATTR-CM by age, sex, hypertension status, and area of residence. The main exposure was a diagnosis of AD within five years preceding the index date (ATTR-CM diagnosis or equivalent for controls). Conditional logistic regression estimated adjusted odds ratios (ORs) for the association between ATTR-CM and AD, accounting for major dementia risk factors including cardiovascular, metabolic, psychiatric, and lifestyle variables. ResultsAmong 96,200 participants (19,240 ATTR-CM cases and 76,960 controls), 28,990 (30.6%) were women, and the mean (SD) age was 82.3 (6.6) years. The adjusted OR for AD among ATTR-CM patients was 0.65 (99% CI, 0.56-0.75), indicating a lower likelihood of AD compared with controls. ConclusionsThis large nationwide study suggests that ATTR-CM is associated with a reduced risk of AD, warranting further investigation into underlying biological mechanisms or possible diagnostic bias.

BackgroundBlood-based biomarkers offer a scalable alternative to cerebrospinal fluid and PET imaging for Alzheimers disease (AD) detection, yet traditional venipuncture limits participation among rural and socioeconomically disadvantaged populations. Self-collection using the Tasso+ capillary device could reduce access barriers, but its feasibility and validity for AD plasma biomarkers remain uncertain, particularly with real-world delays prior to processing. MethodsAdults aged 45-90 years from the Wisconsin SHOW cohort who were underrepresented in AD research (Black or Hispanic race/ethnicity, rural residence, or <bachelors degree) were recruited (n=28). At community "pop-up" clinics participants completed: (1) self-collection of capillary blood via Tasso+; (2) experience surveys; (3) Montreal Cognitive Assessment; and (4) standard venipuncture. To simulate home-based collection and mail return, Tasso+ samples were held at room temperature for 24 hours before centrifugation, whereas venous samples were processed within 30 minutes. Plasma A{beta}40, A{beta}42, A{beta}42/40, GFAP, NfL, and pTau217 were measured on the Quanterix Simoa platform. Between-method agreement was evaluated using Pearson/Spearman correlations, Lins concordance correlation coefficients (CCC), Bland-Altman analyses, and relative bias. Predictors of percent difference were explored with univariate regression. ResultsTasso+ collection was successful for 96% of participants; 64% rated it very easy and 86% reported comfort/no pain, yet 57% preferred future venipuncture--particularly Black, lower-income, and lower-education participants. Agreement varied markedly by biomarker. GFAP and NfL demonstrated excellent concordance (CCC 0.97-0.98) with minimal bias (-6% to -8%). A{beta}40 and A{beta}42 showed modest correlations (r=0.40-0.47) and substantial underestimation (-60% to -70%). A{beta}42/40 and pTau217 exhibited poor correlation and extreme positive bias for pTau217 ([~]+2600%). Hemolysis was more frequent in Tasso+ samples and contributed to disagreement for several markers; processing lag and sample volume were not strong predictors. ConclusionsRemote capillary self-collection with a 24-hour delay is suitable for measuring GFAP and NfL but not currently reliable for A{beta} or pTau217 without improved handling (e.g., temperature control, hemolysis reduction). Although user experience was favorable, trust and logistical concerns limited preference among underrepresented groups. Community-informed strategies and optimized pre-analytics are essential before deploying Tasso+ in large AD studies.

Structured AbstractO_ST_ABSBACKGROUNDC_ST_ABSPatient reports are the standard when examining subjective cognitive decline (SCD). Recent research suggests that informant and clinician reports may also be associated with cognition. This study examined differences between patient, informant, and clinician definitions of SCD and their relationship to cognition. METHODSData from 4290 older adults (n=1690 normal controls, NC; n=840 mild cognitive impairment, MCI; n=1760 Alzheimers disease, AD) were examined from the National Alzheimers Coordinating Center. Linear models examined the relationships between SCD status using the three definitions and cognition at baseline and over time. RESULTSIn NC, informant and clinician SCD were associated with worse cognition at baseline, with patient and clinician SCD associated with worse cognition over time. All definitions were associated with worse cognition at baseline and over time in MCI and AD. DISCUSSIONOur findings suggest the importance of examining different SCD definitions, especially the inclusion of clinician SCD.

BackgroundInnovative treatments for rare diseases often strain healthcare budgets. Precision medicine can improve care and reduce costs by guiding treatment allocation. One example is the forskolin-induced swelling (FIS) assay, which uses patient-derived organoids to predict-response to Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in people with Cystic Fibrosis (pwCF). However, it remains unclear when and for whom this assay adds most value. Therefore, the impact of assay accuracy and target population on health-benefits and costs needs assessment. Research questionTo quantify the impact of sensitivity, specificity and target population on health benefits and costs to inform further development of a predictive assay to guide treatment allocation in pwCF. Study design and methodsAn early economic evaluation was conducted using a decision tree and Markov model. Two strategies were compared over a 40-year horizon: (i) treat all pwCF with CFTR modulators and (ii) predict-response using the FIS assay to guide treatment. Scenario analyses varied assay sensitivity, specificity and treatment responsiveness, reflecting subpopulations of pwCF, including rare CFTR variants. Outcomes included quality-adjusted life years (QALY), false negative rates and costs. Model inputs were based on literature on pwCF with F508del mutations. ResultsThe primary analysis yielded a loss of 1.22 QALYs, with {euro}2,16 million cost-savings per patient in the predict-response strategy. Increasing assay sensitivity reduced QALY loss and false negatives while maintaining cost-savings, while specificity had limited effect on outcomes. Lower treatment responsiveness reduced QALY loss and false negatives while maintaining cost-savings. ConclusionThe assay appears most valuable in pwCF with rare CFTR variants, where treatment response is uncertain. Improving sensitivity is crucial to prevent QALY loss, especially in high-responder populations like pwCF with F508del. The model provides insights into variables impacting personalized testing and serves as a dynamic dashboard to explore scenarios once clinical data becomes available. Key pointsO_LIThis early economic evaluation provides insights in key variables affecting personalized testing to guide CFTR treatment allocation to inform further assay development. C_LIO_LIHigh assay sensitivity is crucial to prevent QALY loss in high responder CF populations, such as pwCF with F508del. C_LIO_LIThe FIS assay appears most value for pwCF with rare CFTR variants and uncertain treatment response. C_LI

ObjectivesThere is a deficit of information available to guide longer-term healthcare planning in meeting health needs and ensuring financial sustainability. This study attempts to address this gap through projecting future population health state and demographics and associated healthcare resources required to satisfy expected demands over the next two decades. MethodsA mathematical model is developed for projecting a populations future age and health state, subject to births, deaths, immigration and emigration. These modelled outputs are combined with healthcare resource utilisation profiles to provide future cost estimates at a total level and for constituent healthcare settings. The model is calibrated to linked longitudinal patient-level data from a one-million-resident NHS healthcare system in England covering a mixture of urban, rural and coastal locations. ResultsCost growth is projected to exceed population growth over the period from 2025 to 2047, with costs growing by 15-22%, depending on the scale of international migration, and the population growing by 4-16%. This is being driven by a projected 15-30% growth in the size of all but the healthiest population health states. If budgets were constrained to population growth, then either a 4% productivity improvement would be required or a 10% reduction in those transitioning to worse health states. ConclusionsAn ageing and unhealthier population is leading to a 5-11% rise in average per-person healthcare costs. To avert this, healthcare administrators may need to prioritise the quicker-acting cash-releasing productivity schemes to fund the prevention measures that may ultimately be required to secure longer-term financial sustainability.

IntroductionAge-group specific disparities for dentalcare use persist in the United States. The COVID-19 led to delays in non-urgent dentalcare. We provide national estimates on dentalcare use and influencing factors for the U.S. population before and during the COVID-19. MethodsWe used nationally representative Medical Expenditure Panel Survey for over pre-COVID-19 years (2018-2019) and COVID-19 years (2020-2021) We estimated yearly survey-weighted trends in mean non-zero dental visits by age followed Poisson regression, controlling for a comprehensive set of confounders across five domains of influence. Dentalcare visits were defined as visits to any dentalcare provider. ResultsOverall analytic sample included non-institutionalized community living persons (unweighted n=6518, weighted N[~]320 million) grouped as ages 0-17, 18-44, 45-64, 65-74 and 75+ present in all four years The prevalence ratio (PR) for dental visits was slightly higher for ages 75+ in comparison to ages 65-74 across years 2018-2021 and increased from 1.73 (95% CI: 1.4, 2.1) to 1.84 (95% CI: 1.5, 2.3) to 2.13 (95% CI: 1.7, 2.7) from 2018 to 2020 but rebounding to near pre-pandemic level in 2021 to 1.66 (95% CI, 1.3, 2.0). Consistent factors during COVID-19 pandemic years 2020-2021 that increased dental visits included dental insurance, high income, and having a usual source of care (p<0.01). ConclusionsDentalcare use rebounded for older adults in 2021 but remained below pre-pandemic levels. Practical ImplicationsIncreasing dentalcare visits across ages remains a key policy priority. Continued monitoring of dentalcare use trends beyond COVID-19 among older adults is critical to improve their oral health.

ImportanceMore than half a decade since the emergence of SAR-CoV-2, its broader sequelae are still poorly understood. Initial data indicate viral infections such as SARS-CoV-2 and herpes zoster negatively impact cognition, but studies examining their independent or synergistic impact on late-onset Alzheimer disease (LOAD) risk among older adults are lacking. ObjectiveTo test the hypothesis that SARS-CoV-2/COVID-19 infection and recombinant zoster vaccination are independently associated with higher and lower risk of LOAD, respectively, among older ([&ge;]65 years of age) individuals. Design, Setting, and ParticipantsA retrospective cohort of 1,480,535 patients from the US National Clinical Cohort Collaborative (N3C) COVID-19 Enclave with no diagnosis of LOAD on January 20, 2020. The follow-up period ended May 16, 2025. ExposureRecorded SARS-CoV-2 infection/COVID-19 and recombinant zoster (Shingrix) vaccination. Main Outcomes and MeasuresLate-onset Alzheimer disease incidence within the five-year follow-up period. ResultsCox proportional hazard models adjusted for age at baseline, sex, and race found that COVID-19 infection was associated with a 12% increased hazard of LOAD (HR=1.12, 95% CI: 1.09-1.15, p<0.0001). Having a Shingrix vaccine did not significantly change the hazard estimate of LOAD (HR=1.13, 95% CI: 1.10-1.16, p<0.0001). Recombinant zoster vaccination was associated with reduced hazard of LOAD in both COVID-19-absent and COVID-19-positive individuals, though the protective effect was attenuated among those with COVID-19 infection. Specifically, among individuals without documented COVID-19 infection, adjusted for age at baseline, sex, and race, Shingrix vaccination was associated with a 37% reduced hazard of LOAD (HR=0.63, 95% CI: 0.60-0.65, p<0.0001), while among COVID-19 patients, the reduction was 23% (HR=0.77, 95% CI: 0.73-0.81, p<0.0001), suggesting a significant interaction between COVID-19 infection and vaccination status on LOAD risk. Conclusions and RelevanceSARS-CoV-2/COVID-19 infection and recombinant zoster vaccination are modifiable risk factors for LOAD among older individuals, with a modestly significant interaction between the two. Recombinant zoster vaccination reduced LOAD risk regardless of sex and race, though the protection is greater in those without documented COVID-19 infection. Recombinant zoster vaccination and reduced exposure to COVID-19 infection in the later decades of life reduce the risk of developing Alzheimer disease over at least a five-year period. Key Points QuestionIs SARS-CoV-2/COVID-19 infection among older individuals associated with late-onset Alzheimer disease (LOAD), and is this risk modified by recombinant zoster vaccination? FindingsRetrospective cohort analysis of older individuals (age [&ge;]65 between January 20, 2020 and May 16, 2025; n[~]1.5 million) indicates that those with [&ge;]1 reported COVID-19 infection were at increased LOAD risk compared with those with no reported infection. Recombinant zoster vaccinated patients had decreased LOAD risk, and among those with a COVID-19 infection, the vaccination mitigated the elevated LOAD risk. MeaningRecombinant zoster vaccination reduces LOAD risk among older individuals and mitigates the COVID-19-associated LOAD risk.

INTRODUCTIONAgitation is a common and burdensome neuropsychiatric symptom in dementia that fluctuates from day to day, but objective tools for short-term risk stratification are limited. We examined whether nocturnal physiological signals from unobtrusive under-mattress sensors predict next-day daytime agitation and whether associations differ for agitation occurrence versus severity. METHODSWe extracted cardiorespiratory, movement, and sleep-proxy features from two long-term care cohorts (N=55; 333 nights) and one external home-monitoring cohort (N=18; 803 nights). A two-part mixed-effects framework was used to model next-day agitation episodes. RESULTSLower nocturnal respiratory rate and greater activity instability independently predicted higher odds of next-day agitation occurrence. Associations were stronger for motor than verbal agitation. Respiration-related predictors were validated externally. Conversely, no nocturnal features significantly predicted agitation severity. DISCUSSIONPassive sleep monitoring identified reproducible, physiologically interpretable markers of next-day agitation occurrence, supporting the potential of under-mattress sensing for short-term risk stratification and more proactive dementia care.

Background Older adults' walking has so far been evaluated using standardised assessments of walking capacity within a clinical setting. By taking the evaluation out of the laboratory into the real world, this study provides first evidence of the ability of Digital Mobility Outcomes (DMOs) to detect changes over time and the Minimal Important Difference (MID) in patients after proximal femoral fracture (PFF). This will guide the implementation of DMOs in research and clinical care. Methods For this multicenter prospective cohort study, 381 community-dwelling older adults were included within one year after sustaining a PFF and assessed at two time points, separated by six months. Walking activity and gait DMOs were measured using a single wearable device worn on the lower back for up to seven days. A global impression of change question and three mobility-related outcome measures (Late-Life Function and Disability Instrument; Short Physical Performance Battery; 4m gait speed) were used as anchor variables. To assess each DMOs ability to detect changes, we calculated the standardized mean change as effect size. For estimating MIDs, both distribution-based and anchor-based methods were applied, followed by triangulation by experts if at least three anchor-based estimates were available per DMO, resulting in single-point estimates. Results All three anchor variables demonstrated substantial changes. Overall, 10 out of 24 available DMOs showed large and 7 DMOs moderate positive effects in the expected direction of the respective anchors. Seven DMOs showed no or only small effects. For 12 DMOs, at least three anchor-based estimates were available, enabling MID triangulation. MIDs for walking activity DMOs per day were: a walking duration of 10 minutes, a step count of 1,000 steps, 50 walking bouts (WB), and 15 WBs in WBs over 10 seconds. For gait DMOs, depending on the walking bout length, MIDs for walking speed were between 0.04 m/s and 0.08 m/s, and MIDs for cadence between 4 and 6 steps/minute. Almost all DMOs showed a strong ability to detect improvement in mobility, but rarely in detecting decline. Conclusions For the first time, MIDs are presented for real-world DMOs in PFF patients. These MIDs inform sample size requirements and interpretation of intervention effects for clinical trials, thereby providing guidance and reassurance for clinicians and regulatory bodies.

BackgroundDementia affects over 57 million people worldwide. UK and international policy position personalised, conversation-based care planning as central to post-diagnostic support. However, delivery in primary care is inconsistent, and many practitioners lack dementia-specific communication training. Existing evidence focuses on single roles or settings, leaving a gap in understanding how communication operates across the primary care workforce. AimsTo identify what helps and hinders effective communication for integrated dementia care planning and determine the support and training needs of the wider primary care workforce. MethodsO_LISemi-structured interviews - 11 people with dementia, 13 family carers, and 19 primary care practitioners from diverse roles, exploring experiences of care planning conversations C_LIO_LIReflexive thematic analysis C_LI ResultsThree themes were developed, progressing from micro-level communication practices (Theme 1: Beyond the tick-box), through triadic dynamics (Theme 2: Balancing voices in the conversation), to organisational influences (Theme 3: From silos to meaningful shared care planning). Time and Conversation as intervention cut across all themes, shaping trust and disclosure. Participants reported reliance on tick box approaches, inconsistent preparation, and uncertainty about care plan purpose and ownership. Non-clinical roles were commonly viewed as well placed to support meaningful conversations, but were often described as constrained by unclear remit and weak integration. ConclusionsA persistent gap remains between policy ambitions and everyday practice. Time-pressured, checklist-driven encounters and fragmented systems undermine shared decision-making. The expanded primary care workforce offers untapped potential to address these gaps, but this requires clearer roles, formal integration, and targeted investment in communicative skills.

BackgroundHigh-dose inactivated influenza vaccination (HD-IIV) demonstrates superior effectiveness versus standard-dose vaccination (SD-IIV) in adults aged [&ge;]60 years. A recent meta-analysis integrated complementary evidence sources of representing over 85 million individuals across 14 influenza seasons. MethodsA previously developed model was updated using life-time horizon and societal perspective. Updated parameters included demographics, costs, hospitalization rates, and relative vaccine effectiveness (rVE): RCT evidence (24% for ILI, 7% for cardiorespiratory hospitalizations) and RCT + real-world evidence (RWE) (15% for ILI, 8% for cardiorespiratory hospitalizations). ResultsHD-IIV resulted in incremental cost-effectiveness ratios of {euro}7,300/QALY (RCT evidence) and {euro}5,800/QALY (RCT+RWE evidence). Implementation would prevent 7,200 general practitioner visits, 6,300 cardiorespiratory hospitalizations, and 269 deaths, by using RCT evidence. Probabilistic sensitivity analysis demonstrated >99% probability of cost-effectiveness at {euro}20,000/QALY threshold for both RCT and RCT+RWE evidence. ConclusionsHD-IIV remains highly cost-effective for Dutch adults aged [&ge;]60 years under updated evidence scenarios, supporting implementation in the national immunization programme. HighlightsO_LIThe economic analysis of high-dose inactivated influenza vaccine was updated. C_LIO_LIRelative vaccine effectiveness of HD-IIV incorporating recent evidence was used. C_LIO_LIHD-IIV remains cost-effective in Dutch adults aged [&ge;]60. C_LI

ObjectivesNon-communicable diseases (NCDs) account for almost 90% of deaths in Europe, yet comparative estimates of the productivity costs associated with premature NCD mortality across diseases and countries remain limited. This study estimates and compares productivity losses attributable to cardiovascular disease (CVD) and cancer mortality among working-age populations across Europe. Population-based data were used to estimate productivity costs for CVD and cancer deaths across 30 European countries. Sex- and age-specific mortality data for 2021 were obtained from the World Health Organization Mortality Database. Economic data, including wages, unemployment rates, and labour force participation rates, were sourced from Eurostat. Productivity losses were valued using a human capital approach incorporating an age-transition lifecycle simulation model that adjusts for lifetime wage trajectories and labour market dynamics. Costs were discounted at 3.5%. Total productivity losses from cancer and CVD mortality in working-age populations were estimated at {euro}195.7 billion, equivalent to 1.24% of European GDP. Cancer accounted for 62.5% ({euro}122.2 billion) of total productivity losses, while CVD accounted for 37.5% ({euro}73.5 billion). Total CVD-related productivity costs exceeded cancer-related costs in Central and Eastern Europe, whereas cancer productivity costs were higher in Western, Northern, and Southern Europe. Mean productivity costs per death were higher for CVD ({euro}219,848; 95% CI 165,241-270,247) than for cancer ({euro}217,744; 95% CI 166,554-273,144). A larger gender gap was observed for CVD mortality, with a male-to-female cost ratio of 2.5 compared with 1.6 for cancer. Productivity losses associated with premature cancer and CVD mortality represent a substantial economic burden across Europe, with pronounced variation by disease, region, and sex. These findings provide comparative, cross-country estimates of the human capital costs associated with major NCD causes of death.