Journal of the American Medical Directors Association

Introduction: End of life decision making poses unique challenges for individuals with dementia and their family caregivers as cognitive decline shifts decision making responsibility to surrogates. Methods: Using 2010 to 2022 Health and Retirement Study (HRS) exit interview data, we compared advance directive completion, decision making needs near death, involvement of others in decision making, and concordance between expressed preferences and care received among decedents with and without dementia. Analyses incorporated HRS exit interview sampling weights, primary sampling units, and strata to account for the complex multistage probability design of HRS and produce nationally representative estimates of U.S. older adult decedents (50 years or older). Weighted descriptive statistics and design adjusted Wald tests were used to compare groups. Results: Among 5,389 decedents, 1,010 (weighted 17.7%) had dementia prior to death. Decedents with dementia were more likely to have completed advance directives than those without dementia (81.3% vs. 69.1%, p<.001). However, they also had significantly higher decision making needs in the final days of life (54.3% vs. 47.2%, p<.001). Children or grandchildren were more frequently involved in care decisions for decedents with dementia (63.9% vs. 45.6%, p<.001). Despite differences in decision making processes, most decedents in both groups expressed preferences for comfort focused care, and preference care concordance exceeded 90% in both groups. Conclusions: Findings suggested that dementia reshaped the structure and intensity of the shared decision making process by increasing surrogate engagement and decisional demands, underscoring the importance of early advance care planning and structured support for family caregivers to sustain goal concordant care.

Background: Wheeled walkers can improve safety during walking, but improper use may increase fall risk among frail older adults. No suitable tool exists to assess safe indoor wheeled walker use in this population. This study aimed to develop and validate a video-based expert assessment tool. Methods: Based on the literature and expert consensus, seven problematic indoor situations were identified, and an assessment tool with five safety criteria per situation was developed (maximum score = 35). Fifty participants (mean age 83.9 years, 64% women) from a geriatric rehabilitation clinic and a nursing home were video-recorded while using a rollator. Expert ratings were compared with nursing staff ratings, self-ratings, and the Timed Up and Go test to evaluate validity. Intra- and inter-rater reliability were determined from independent ratings by two physiotherapists and a repeated expert rating after seven days. Sensitivity to change was assessed after two weeks of rehabilitation, and feasibility by the time required for assessment. Results: The expert score of rater 1 at baseline was 28.5 points, and assessment required a mean of 17.5 minutes. Intra-rater reliability was excellent (ICC = 0.98) and inter-rater reliability was good (ICC = 0.80). Validity analyses showed the strongest association with nursing staff assessments (r = 0.74) and a moderate association with the Timed Up and Go test (r = -0.45). After two weeks, patients improved by an average of 2.38 points (8.4% of baseline score). Conclusions: The new instrument demonstrated high reliability, acceptable validity, sensitivity to change, and good feasibility for assessing safe wheeled walker use in frail older adults. Trial registration number and date of registration: DRKS00038358, 07/11/2025

Background: Sleep problems are common in older people and have been associated with increased fall risk, but the mechanisms underlying this relationship remain unclear. Gait quality reflects balance control and neurological function and may provide insight into pathways linking sleep health and falls. Methods: Data from 758 community-dwelling older people ([&ge;]65 years; mean age 75.8 years, 69.3% women) were analysed. Sleep problems were assessed at baseline using a self-reported item (Patient Health Questionnaire-9, question 3). Daily-life gait quality and habitual walking speed were derived from one week of wearable sensor monitoring. Falls and injurious falls were prospectively recorded over 12 months. Associations between sleep problems, gait quality, and fall incidence were examined using regression models adjusted for demographic, pain and cognitive factors, and use of sleeping medication. Results: Sleep problems were reported by 43.9% of participants. Sleep problems were not associated with habitual walking speed, but were associated with lower gait quality in daily life (adjusted {beta} = -0.15, 95% CI -0.27 to -0.03). Participants reporting sleep problems had higher incidence rates of total falls (adjusted IRR = 1.42, 95% CI 1.07 to 1.90) and injurious falls (adjusted IRR = 1.50, 95% CI 1.07 to 2.10). Conclusions: Self-reported sleep problems were associated with impaired real-world gait quality and substantially higher rates of falls and injurious falls in older people. These findings suggest that sleep problems may increase fall risk by altering balance control rather than by reducing walking speed. Sleep should be considered when managing fall risk, and fall risk should be considered in older people with sleep complaints.

BackgroundActivities of Daily Living (ADL) assessments are essential outcome measures in rehabilitation and long-term care, but primarily focus on task completion and provide limited insight into the postural control structures underlying movement failure. This paper proposes the Four Movement Screen Structure (4MS), a theoretical framework that reconceptualizes human movement control through four postural control phases: supine, sitting, standing, and single-leg standing. The framework proposes that functional decline may present with non-continuity, asymmetry, and compensatory preservation, rather than a simple reversal of motor development. MethodsAn exploratory, hypothesis-generating cross-sectional study was conducted with 297 certified care recipients (mean age 80.5 years) across multiple day-service facilities in Japan. Each participant was assessed using both the Barthel Index (BI) and the 4MS evaluation. Descriptive statistics, Pearson correlations, chi-square tests, and Fishers exact tests were used to explore the structural properties of the framework. ResultsThe mean BI total was 89.0 (SD = 13.8); the mean 4MS total score was 7.75 (SD = 2.02). A moderate positive correlation was found between BI total and 4MS total score (r = 0.471, p < 0.001, 95% CI [0.378, 0.555]). Of the five defined decline types, four were observed: mixed (57.6%), supine-dominant (21.2%), standing-dominant (5.7%), and single-leg-dominant (15.5%); sitting-dominant was not observed. The supine phase was the primary intervention target in 74.4% of cases--a finding we term the "supine paradox." In a subsample of 274 participants, 90.0% of those in the low supine score group (0-1.0, n = 170) performed rising from supine independently, suggesting that this paradox reflects qualitative deficits in foundational motor control masked by compensatory strategies. ConclusionsThese exploratory findings are broadly consistent with the non-reversal hypothesis and suggest that 4MS may capture structural dimensions of postural control not fully represented by conventional ADL assessment. As a hypothesis-generating study, these findings should be interpreted as generating testable hypotheses for future longitudinal and interventional research. Keywords: Postural control; Activities of daily living; Motor development; Functional decline; Barthel Index; Long-term care; Supine paradox; Non-reversal hypothesis; Geriatric assessment; Exploratory study

Background: Advance care planning (ACP) documentation, including living wills and durable power of attorney (DPOA), is intended to support goal concordant end of life care. However, it is unknown if comprehensive documentation confers additional benefits, and how these associations vary across clinical contexts. Methods: We used 2010 to 2022 Health and Retirement Study exit interview data to examine associations between ACP documentation and end of life care among U.S. adults aged 50 years and older. Documentation was categorized as none, one document (living will or DPOA), or two documents (both). Outcomes included intensive care unit (ICU) use, life sustaining treatment, hospice enrollment, and out-of-hospital death. Modified Poisson regression models were used to estimate adjusted risk ratios (aRRs), and temporal trends in documentation were assessed using joinpoint regression. Results: Among 5,622 decedents representing 23.2 million individuals, 42.7% had two documents and 28.9% had none, documentation increased substantially around 2014. Compared with no documentation, having any documentation was associated with lower likelihood of life-sustaining treatment (aRR=0.85, 95% CI: 0.74 to 0.98) and higher likelihood of hospice enrollment (aRR=1.43, 95% CI: 1.28 to 1.60) and out-of-hospital death (aRR=1.11, 95% CI: 1.06 to 1.18), but not ICU use. Having two documents showed similar patterns, with modest differences compared with one document after adjustment. Associations were stronger among decedents with expected death and attenuated among those with unexpected death. Conclusions: Comprehensive ACP documentation is associated with less aggressive end of life care and greater hospice use, though the incremental benefits of two documents are modest. Findings highlight the importance of documentation within care planning processes and the clinical context.

Aim(s)To describe adult palliative and end-of-life care provision by community health nursing services using a: O_LINational dataset (2013-2024) to report patterns in service provision over time. C_LIO_LIRegional dataset (2022/23, 2023/24 and 2024/25) to describe palliative and end-of-life care activities. C_LI DesignSecondary analyses of existing national and regional datasets. MethodsWe used national data to describe the populations served; workforce; referrals; unique service users seen annually; contacts; time on caseload; care delivered/care locations; support to other teams/processes; and deferred care. Regional data was used to examine palliative and end-of-life care activities in the context of all nursing care delivered. ResultsNationally, referrals to community health nursing services increased steadily from 4,000 to 6,000 per 100,000 weighted population between 2013 and 2024, while unique service users remained stable (around 2,600-2,800). Median average time on caseload reduced markedly from over 150 days to around 50 days, despite stable contact frequency (median 23 total contacts per service user) and duration (median 26 minutes for face-to-face contacts). Regional data showed that palliative and end-of-life care consistently accounted for 9.6% of all community nursing clinical time (30-32 hours per 1,000 population annually) across three years, even as total care hours declined. A disproportionate amount of palliative and end-of-life care occurred out-of-hours. ConclusionIncreasing referrals and shorter time on caseloads indicate a system under pressure. Time spent on palliative and end-of-life care by community health nursing teams has remained stable over time, despite growing population need. Workforce capacity, skill mix, and out-of-hours provision need to align to support high-quality, person-centred care in the community. Implications for the profession and/or patient careThis evidence informs better planning to ensure sufficient provision and workforce in community health nursing. Patient and public contributionPatients, family carers and public members contributed to interpreting findings and implications for practice. What does this paper contribute to the wider global clinical community?O_LIProvides combined national and regional data to describe the scale and nature of palliative and end-of-life care delivered by community health nursing services over time. C_LIO_LIFindings give a detailed picture of how community health nursing services are under pressure because of increasing referrals and being required to deliver a greater breadth of tasks. C_LIO_LIModels of community health nursing are changing with shorter care episodes and significant palliative and end-of-life care workload (with distinctive challenges out-of-hours). C_LI

BackgroundDemand for community-based end-of-life care is rising globally, driven by ageing populations with increasingly complex needs. Community nurses have a central role in providing end-of-life care, yet the proportion of their time spent in supporting people in their final year of life remains unclear. AimsTo investigate how much of community nurses daily work involves caring for people in their last year of life, and the extent to which end-of-life care visits are cancelled, deferred or undertaken to unsatisfactory standards. DesignAnonymous online survey and multimethod analysis. Setting/participantsUnited Kingdom survey of community nurses, circulated via professional networks, social media and snowball sampling, between 28 April and 27 June 2025. ResultsA total of 1,471 nurses responded. Most worked in community and district nursing services (78.6%, 1156/1471) or specialist palliative care services (11.8%, 174/1471). Community and district nurses spent 23.5% (median) of their last shift providing end-of-life care. Over one in ten respondents (11.6% (171/1471) reported deferring at least one end-of-life visit during their last shift. Specialist palliative nurses were twice as likely to defer visits compared to community and district nurses (OR=2.48, 95% CI: 1.63-3.72, p<0.001). Staff shortages, demand exceeding capacity, and other systematic barriers contributed to deferring visits. ConclusionsCommunity nurses play a vital role in end-of-life care, yet some of this important patient care is left undone or deferred. Investment in core and specialist nursing services, with efforts to enable and sustain this workforce, is urgently needed to meet globally growing demand for community-based end-of-life care. What is already known about the topic?O_LIDemand for community end-of-life care is growing in many countries. C_LIO_LICommunity nurses play a key role in end-of-life care, yet the volume and complexity of their daily work supporting people in the last year of life remains poorly understood. C_LI What this paper addsO_LINurses working in community and district nursing services spent a median of 23.5% of their last clinical shift providing end-of-life care. C_LIO_LIHalf (52%) of respondents who provided end-of-life care during their last shift reported delivering one or more aspects of this care below their professional satisfaction, due to workload and capacity issues. C_LIO_LIOver one in ten (11.6%) of nurses reported having deferred or cancelled end-of-life care visits on their last shift, significantly more specialist palliative care nurses (24%) than community and district nurses (10.4%). C_LI Implications for practice, theory or policyO_LIOur findings reveal a notable proportion of deferred and cancelled end-of-life care visits and care not undertaken to nurses professional satisfaction. C_LIO_LISustained, intentional investment in core and specialist nursing services, together with improved system-wide integration, is needed to support this vital workforce. C_LIO_LIFurther research is necessary to understand how community and district nurses and specialist palliative care nurses can most effectively prioritise end-of-life care within finite resources and competing demands. C_LI

ContextIn the UK, and in other countries, people living with a terminal illness are eligible for financial support to help with the costs of serious illness and to support their dignity and independence. This study investigates the take-up of benefits in the last year of life and identifies sociodemographic, clinical, and geographical factors associated with underclaiming. MethodsRetrospective cohort study using linked mortality, Census and benefits data for all people who died aged 16+ from chronic illnesses in England and Wales between 1 May 2018 and 30 April 2021. Outcome was receipt of non-means tested disability benefits in the last 12 months of life. We describe geographical variation in take up, and association with sociodemographic, clinical and geographical exposures using Poisson models. FindingsOur population included 1,049,493 eligible decedents, with an overall take-up rate of 65.9%. After adjusting for sociodemographic factors, variation in take-up by cause of death was wide: liver disease 44% (95% CI 43-45%), heart failure 52% (51-52%), cancer 62% (61-62%), dementia 75% (74-75%), and neurodegenerative diseases 90% (88-91%). Across Local Authorities, the age-and-sex-standardised take-up varied from 53% to 78%; rates were generally higher in more deprived areas, but not uniformly. ConclusionsIn England and Wales, 1 in 3 people who die from expected causes (120,000 each year) do not receive the benefits for which they are eligible. Our analysis uses novel data linkages and highlights clinical and sociodemographic groups and geographical areas that could be targeted with proactive take-up initiatives.

BackgroundEarly recognition of dementia-related changes is critical for timely intervention. The AD8 Dementia Screening Interview (AD8) detects subtle cognitive and functional changes, yet its broader associations with health and wellbeing among Chinese-speaking older adults remain underexplored. MethodsA cross-sectional study was conducted with 144 community-dwelling Chinese older adults (mean age 73.1 years; 81.3% female). Participants completed sociodemographic, health, functional, and psychosocial measures, including the AD8 and the Geriatric Depression Scale (GDS-15). Exploratory Factor Analysis (EFA) assessed the dimensionality of the AD8, and binary logistic regression examined associations between AD8 items and demographic, health, functional, and psychosocial outcomes. ResultsChronic disease was prevalent (68.1 percent), and 13.2 percent reported a mental health disorder. EFA identified three domains: memory impairment, executive and interest decline, and functional recall difficulties, explaining 61.7 percent of the variance. Logistic regression showed predictive roles for judgment problems (AD8_1), repetition (AD8_3), financial difficulties (AD8_6), tool-use difficulties (AD8_4), and daily memory problems (AD8_8). Financial and executive difficulties were associated with age and mobility challenges, while repetition predicted psychological disorders and hopelessness. Judgment problems were linked to lower life satisfaction and happiness but greater helplessness. Worthlessness was predicted by financial, tool-use, and memory difficulties, whereas intact temporal recall (AD8_5) was protective. Several outcomes including boredom, low energy, and staying home were not significant. ConclusionDistinct AD8 items predicted vulnerabilities across physical, psychological, and social domains. Findings highlight the multidimensional value of the AD8 as a culturally relevant screening and risk stratification tool for community-based assessments of Chinese older adults. Summary Statement Implications for PracticeO_ST_ABSWhat does this research add to existing knowledge in gerontology?C_ST_ABSThis study shows that specific AD8 items identify early multidimensional vulnerability among community-dwelling Chinese-speaking older adults. Difficulties with judgment, repetition, financial management, tool use, and daily memory were associated with functional limitations and psychosocial distress, extending the AD8 beyond dementia screening alone. The identification of three AD8 domains supports a broader understanding of early cognitive change as involving cognitive, functional, and emotional processes. The findings contribute culturally specific evidence from an under-researched population in gerontological research. What are the implications of this new knowledge for nursing care with older people?For nursing practice, the AD8 provides a brief, feasible tool to support holistic assessment in community and aged care settings. Key AD8 indicators can guide nurses in identifying older people at risk of functional decline and emotional vulnerability, enabling earlier, person-centred interventions. The findings highlight the importance of culturally and linguistically appropriate assessment when caring for diverse ageing populations. How could the findings be used to influence policy or practice or research or education?The results support integrating brief cognitive screening into routine nursing assessments and community-based aged care services to promote early identification and ageing in place. Nursing education should emphasise interpreting cognitive screening within psychosocial and cultural contexts. Longitudinal research is needed to assess intervention effectiveness. Key Points[tpltrtarr] Early cognitive changes matter for older Chinese-speaking adults, because difficulties with judgment, repetition, financial management, and tool use (AD8 domains) were consistently linked to poorer functional and psychosocial outcomes. [tpltrtarr]Beyond dementia screening, the AD8 proved useful for detecting vulnerabilities in wellbeing and daily functioning, extending its role beyond diagnostic sensitivity. [tpltrtarr]A cultural focus is vital, as this study is among the first to examine AD8 associations in older Chinese-speaking adults, underscoring the need for culturally tailored screening. [tpltrtarr]The psychosocial impact of cognitive changes was evident, with strong associations to helplessness, worthlessness, and reduced life satisfaction, reinforcing the overlap between cognitive and emotional health. [tpltrtarr]In practice, integrating AD8 screening into community and primary care could help identify at-risk individuals early and support targeted interventions in culturally and linguistically diverse populations.

Background Low-level systemic inflammation has been associated with late-life depressive symptoms. Whether individuals with higher inflammation derive preventive benefit from low-dose aspirin therapy is unknown. Methods We performed a post-hoc analysis of the ASPiring in Reducing Events in the Elderly (ASPREE) randomised, double-blind, placebo-controlled trial. Baseline C-reactive protein (hsCRP) was measured in plasma and depressive symptoms were assessed annually using the Center for Epidemiologic Studies Depression 10 Scale with elevated symptoms defined as CES-D-10 >= 8. Participants with elevated depressive symptoms at baseline were excluded. We fitted population-averaged logistic generalised estimating equation models adjusted for baseline sociodemographic and lifestyle covariates, including an hsCRP x treatment interaction to test effect modification by aspirin. Results Higher baseline hsCRP was associated with increased odds of elevated depressive symptoms during follow-up (OR 1.07 per SD increase in hsCRP, 95% CI 1.03-1.11). Low-dose aspirin allocation did not modify the hsCRP-depressive symptoms association (interaction OR 1.02, 95% CI 0.94-1.10). Findings were similar after additional adjustment for comorbidity and other covariates. Conclusions In community-dwelling older adults during the ASPREE randomised trial period, higher baseline hsCRP was modestly associated with elevated depressive symptoms. There was no evidence that low-dose aspirin was associated with reduced risk of depressive symptoms among participants with higher baseline inflammation.

Background: People affected by dementia experience intersecting care inequalities. We explored relationships between ethnicity and health and social care resource use among people with dementia in an ethnically diverse urban region. Methods: We conducted a retrospective observational cohort study using Discover-NOW, including patients with dementia between 1.4.2015 and 1.4.2025. We calculated ethnic density as the percentage of the Middle Layer Super Output Area (SOA) population self-identifying with the same ethnic group. Regression models, clustered by Local SOA, tested whether ethnic density moderated relationships between ethnicity and primary care, outpatient, inpatient, emergency and social care service use, controlling for sociodemographic characteristics, deprivation, comorbidities and time of diagnosis. Findings: We included 30,704 people with dementia. People from Black and Mixed ethnic groups used more primary care, and those from Asian ethnic groups less primary and secondary care, than White ethnic groups. Rates of local authority social care packages were similar across ethnic groups. High ethnic density predicted fewer GP consultations in Black ethnic groups, but more in South Asian groups. Interpretation: Among Black ethnic groups, primary care use was relatively high, especially in areas of low ethnic density, perhaps reflecting greater needs among communities at risk of racism and isolation. The trend towards increased primary care use among South Asian people in areas of higher ethnic density may reflect communities mitigating help-seeking hesitancy related to cultural and language barriers. Greater care integration could reduce care inequalities among minority ethnic communities who may experience fewer barriers to social relative to health care.

Aims. The risk of cognitive decline after losing a spouse remained mixed. This study aims to investigate the association between spousal loss and risk of cognitive decline, assess whether this association varies by sex and age, and identify modifiable factors. Methods. We conducted a prospective cohort study using harmonized data from six population-based aging surveys: the US Health and Retirement Study and its sister surveys in England, Mexico, China, India, and South Africa, incorporating their respective Harmonized Cognitive Assessment Protocol (HCAP) sub-studies. Spousal loss (yes vs no) was the exposure. Cognitive outcomes (i.e., orientation, memory, executive function, and language), were assessed using HCAP neuropsychological batteries. We conducted parallel analyses in six cohorts. Associations between spousal loss and cognitive outcomes were estimated using generalized linear models, and summarised estimates were derived via random-effects meta-analyses. Sex stratification and restricted cubic spines were used to examine how these associations vary by sex and age, respectively. Results. The analytical cohort consisted of 18,551 individuals aged 61.22 (SD 6.30) to 71.37 (SD 7.33) years. Widowhood prevalence ranged from 14.1% in CHARLS to 53.9% in HAALSI and was consistently higher in women. Spousal loss was associated with poorer memory (multivariable-adjusted {beta} = -0.07, 95% CI -0.12 to -0.01) and executive function (multivariable-adjusted {beta} = -0.08, 95% CI -0.13 to -0.03) in the meta-analysis, with no significant associations for orientation or language. While results were generally consistent in five cohorts, the ELSA showed divergent patterns (orientation: {beta} = 0.10, 95% CI 0.06 to 0.13; memory: {beta} = 0.05, 95% CI 0.02 to 0.08; language: {beta} = 0.16, 95% CI 0.12 to 0.19). Sex-stratified analyses indicated poorer executive function among men (multivariable-adjusted {beta} = -0.14, 95% CI -0.19 to -0.08) and poorer memory among women (multivariable-adjusted {beta} = -0.07, 95% CI -0.14 to -0.01) following widowhood. Nonlinear age-related effects on cognition were observed in ELSA, LASI, and HAALSI. Higher education, internet use, and BMI were negatively associated with the risk of cognitive decline among widowed participants. Conclusions. Spousal loss is associated with domain- and sex-specific differences in cognitive performance, with substantial heterogeneity across study populations. Future research should integrate biopsychosocial markers to develop context-sensitive interventions for widowed older adults.

Burn trauma disproportionately impacts older adults, yet existing burn severity models emphasize age, total body surface area (TBSA), and inhalation injury without accounting for geriatric-specific vulnerabilities such as frailty. We conducted a retrospective cohort study of 326 geriatric patients admitted with burn injuries between 2020 and 2024 to evaluate how TBSA, burn location, inhalation injury, renal insufficiency, comorbidities, and functional dependence in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) affect in- hospital mortality and discharge disposition. Based on multivariable logistic regression and chi- square analyses, TBSA, as expected, emerged as the strongest predictor across models. Each 1% increase in TBSA was associated with a 7% increase in the odds of in-hospital mortality (p=0.006) and a 12 to 19% increase in odds of post-acute care placement (p<0.001). Inhalation injury and renal insufficiency were also independently associated with increased odds of both mortality and post-acute care disposition, whereas respiratory comorbidity predicted mortality alone. Functional status demonstrated outcome-specific prognostic value: ADL dependence predicted mortality, while IADL dependence predicted discharge disposition. Patients with some ADL dependence had five-fold higher odds of in-hospital mortality (p=0.011), while some (OR=2.48, p= 0.039) and full IADL dependence (OR=2.61, p=0.025) were associated with higher odds of post-acute care placement. Integrating structured functional assessments that distinguish basic from instrumental limitations alongside established burn severity metrics may enhance prognostication and guide individualized care planning for older adults with burn injuries.

Alzheimers Disease and Related Dementias (ADRDs) are linked to reduced bone integrity and increased fracture risk, but the mechanisms that underlie this risk remain poorly defined. Current research suggests that environmental factors, such as diet, sleep, and light exposure can modulate the brain-bone axis, increasing susceptibility to bone loss and fractures. Circadian disruption (CD) associated with ADRDs may exacerbate the effects of disease and aging in the bone. In particular, regulation of bone marrow progenitors may be acutely susceptible to disruption along this axis. Here, we explore the interplay among genetic and environmental factors that influence bone structure, marrow progenitor cell activity, and monocyte-derived macrophages. The APP/PS1 transgenic mouse model (AP) is used as an in vivo model of amyloid-beta deposition. High-resolution micro-computed tomography (CT) identified sex- and genotype-specific responses in trabecular morphometry. Follow-up analysis with Raman spectroscopy (RS) found accumulation of non-enzymatic modifications of the organic matrix and notched three-point bending identified concomitant loss of bone toughness due to both CD and AP. Single-cell RNA sequencing (scRNA-seq) confirmed the presence of oxidative stress signals in the cellular populations of the bone marrow. We further mapped significantly differentially expressed genes (DEGs) from monocytes in the bone marrow to circadian-regulated proteins in monocyte-derived macrophages, revealing dysregulation of circadian timing in macrophages in vitro. These findings offer new insights into how environmental disruptions can exacerbate the progression of neurodegenerative disease and bone degradation. LAY SUMMARYPatients with Alzheimers disease have an increased bone fracture risk, but the biological link between brain and bone disease is not well understood. Everyday factors such as altered light exposure (shift work, screens late at night, etc.) can worsen outcomes in the brain and skeleton. Using a mouse model of Alzheimers disease, we found that both genetic risk and circadian disruption contribute to weaker bone and altered bone quality. We also identified inflammation and stress responses in bone marrow cells, suggesting that bone marrow may play a key role in linking brain disease to bone fragility.

BackgroundAcceptance of death is an important aspect of a good death and an indicator of high-quality palliative care. Limited evidence exists on the extent to which patients accept their approaching death and which socio-demographic or end-of-life care characteristics are associated with acceptance, in both cancer and non-cancer patients. MethodsWe conducted a retrospective cross-sectional survey in representative GP networks in the Netherlands and Italy (2013-2015), and Belgium and Spain (2013-2014). GPs registered all deceased adult patients in their practice, reporting health and care characteristics in the last three months of life and the level of acceptance of approaching death on a four-point scale ("1. Yes, completely" to "4. No, not at all"). Non-sudden deaths were included, totaling 2,796 patients (1,474 cancer; 1,322 non-cancer). ResultsAcceptance was recorded for 97% of patients (n=2,713), of which 17% were assessed as unknown. GPs assessed that 30% of patients had complete acceptance, with similar proportions in cancer and non-cancer patients (30% vs 29%). Multivariable logistic regression showed that older age (OR 1.03, 95%CI 1.02-1.04, p<0.01), country (OR 0.27 Belgium, OR 0.11 Italy, OR 0.10 Spain; reference: Netherlands), and palliative care by the GP until death (OR 1.39, 95%CI 1.07-1.79, p<0.01) were independently associated with complete acceptance. ConclusionSocio-demographic, contextual, and end-of-life care factors influence GP-assessed acceptance of approaching death, whereas a cancer diagnosis does not. These findings emphasize the importance of culturally sensitive, age-appropriate, and palliative care-oriented approaches to support patient acceptance at the end of life.

ImportanceAdverse neighborhood conditions can lead to poorer health outcomes, potentially through accelerated biological aging. However, whether these relationships are explained by individual- or neighborhood-level factors remains unclear. ObjectiveTo examine the association between neighborhood deprivation, measured by the Area Deprivation Index (ADI), and epigenetic age acceleration and assess whether individual- and neighborhood-level characteristics mediate or modify these associations. DesignCross-sectional study using data from a Yale Stress Center study between 2008 and 2012. Data analysis was conducted from July 2025 to January 2026. SettingCommunity-based sample from the greater New Haven, CT area. ParticipantsA total of 370 healthy adults aged 18 to 50 years without major psychiatric, medical, or cognitive disorders who provided blood samples for DNA methylation analysis. Main Outcomes and MeasuresEpigenetic age acceleration measured from DNA methylation using four second-generation epigenetic clocks, with associations assessed among aging, neighborhood deprivation, and individual- and neighborhood-level factors. ResultsData were analyzed from 370 participants (212 women [57.3%], 158 men [42.7%]; mean [SEM] age, 29.3 [0.46] years). Greater neighborhood deprivation was associated with greater lifetime adversity ({beta}=0.112, p<.001) and lower educational attainment ({beta}=-0.019, p=.012), and accelerated epigenetic aging as measured by GrimAge ({beta}=0.037, p<.001), PCGrimAge ({beta}=0.019, p<.001), and PCPhenoAge ({beta}=0.041, p<.001), but not PhenoAge (p=.23). In multivariable models accounting for individual factors, neighborhood deprivation remained associated with these three clocks. Lifetime adversity partially mediated the association between ADI and accelerated GrimAge (20.3% of total effect) and PCGrimAge (23.3%). Race moderated the direct association between ADI and epigenetic aging, with stronger associations between neighborhood deprivation and accelerated GrimAge ({beta}=0.061, p=.004) and PCPhenoAge ({beta}=0.057, p=.02) observed among Black participants compared to White. ConclusionsGreater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks, with lifetime adversity partially mediating these associations. Stronger effects were observed among Black participants. These findings suggest that neighborhood environments and cumulative stress may contribute to biological aging and racial disparities in aging trajectories. Key PointsO_ST_ABSQuestionC_ST_ABSIs neighborhood deprivation associated with epigenetic age acceleration, and if so, how do neighborhood- and individual-level factors impact this relationship? FindingsIn this cross-sectional study of 370 adults, greater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks. Lifetime adversity partially mediated these associations, and the relationship between neighborhood deprivation and accelerated aging was stronger among Black participants than White participants. MeaningThese findings suggest that neighborhood conditions and lifetime stress contribute to accelerated biological aging and suggest that epigenetic aging may represent one biological pathway through which neighborhood-level racial inequalities contribute to health disparities.

Background Slow walking in older adults with mild parkinsonian signs (MPS) is a complex, multifactorial phenomenon arising from the cumulative burden of subclinical age-associated pathologies. This decline reflects age-associated neuronal loss in the dopaminergic system. A recent study suggests that levodopa treatment may enhance gait parameters. The goal of this small pilot study is to explore the effect of levodopa treatment on slow walking gait in older adults with MPS. Method This study was a randomized, placebo-controlled clinical pilot trial. Slow walking older adults without clinical evidence of PD were recruited and randomized into 2 groups (active treatment group or placebo control group). Participants in the active group were pre-treated with carbidopa for three days, followed by carbidopa-levodopa for seven days. Spatiotemporal gait parameters were evaluated at baseline and post-intervention. Results Gait factor analysis identified three main factors explaining gait characteristics at baseline, which included gait efficiency, gait rhythmicity, and gait turning.No effect of treatment was observed in the placebo group (p=0.111, p=0.616), no group difference was observed between the placebo and active group at baseline ({beta}=0.310, p=0.547), but a strong trend for a treatment-related increase was observed in the active treatment group ({beta}=0.506, p=0.076). Conclusion Our preliminary data suggest that sustained levodopa treatment (one week) in conjunction with carbidopa pre-treatment and concomitant carbidopa supplementation is feasible in slow walking older adults with MPS. Moreover, the data indicate potential efficacy, showing improvements in cadence, and step durations.

ObjectiveTo examine whether menopausal women who initiate systemic menopausal hormone therapy (MHT) around menopause (45-60 years old) have a different risk of developing dementia than those not taking MHT. DesignSystematic review and meta-analysis of randomised controlled trials and longitudinal observational studies. Risk of bias was assessed using ROB-2 and ROBINS I-V2. Data sourcesMEDLINE, Web of Science, EMBASE, and Cochrane Library to 27 March 2026. Eligibility criteria for selecting studiesStudies which measured dementia or cognitive decline in women who initiated systemic MHT between ages 45-60 or within 5 years of menopause, compared with placebo or no MHT. Authors contacted for additional details if needed. Main outcome measuresDementia, Alzheimers disease (AD), cognitive decline. Results10 studies totalling 213,678 participants (189,525 in studies with the primary population). There was no significant increased risk in women with a uterus for all cause dementia (pooled hazard ratio (HR): 1.12; 95% CI 0.91-1.31, N=78,613, I2 = 96.9%), but increased AD risk (HR: 1.14; 95% CI 1.02, 1.29, N=134,865, I2 = 35.6%). Results were similar in sensitivity analyses including women with or without a uterus. Results for cognitive decline were variable. ConclusionsMHT initiated around the age of menopause should not be prescribed for cognition or dementia prevention. It is not protective against dementia and may increase risk slightly. The magnitude of risk was similar in AD and dementia, but the latter with larger confidence intervals. Studies which followed up individuals rather than on health records lost people to follow up. This may account for difference in cognitive decline outcomes between studies, as people with cognitive impairment and dementia are more likely not to attend. MHT prescribing should balance benefits against risks, including evidence of a small increased dementia risk. There are few high-quality studies, so further research would inform recommendations. Systematic review registration Prospero CRD420251010663 What is already known on this topic?O_LIMenopausal hormone therapy (MHT) is effective for alleviating vasomotor symptoms. Contemporary guidelines recommend treatment should be initiated for such symptoms under age 60 and or within 10 years of menopause onset. C_LIO_LIA large randomised trial on the topic found increased risk of dementia in women initiating MHT after the age of 65. C_LIO_LIIt is unknown whether initiating MHT around the age of menopause impacts the risk of dementia or cognitive decline. C_LI What this study addsO_LIThere was no evidence that taking MHT around the time of menopause decreases the risk of dementia or cognitive impairment. C_LIO_LIThey should not be prescribed for these indications. C_LIO_LIWe were able to find more studies which examine this question by contacting authors for additional data. C_LIO_LIInitiating MHT in women with a uterus around the age of menopause increased the risk of Alzheimers disease slightly, by over 10%, and there is a similar but not significant effect in the fewer studies of all cause dementia. Women with or without a uterus show similar results. C_LIO_LIWe found no significant difference shown in cognitive decline, possibly due to loss to follow up. This may be because most studies of cognitive decline follow up C_LI

Background: Evidence regarding dementia prevention strategies has been accumulating. However, disseminating research findings to the public is often difficult, and addressing the evidence-practice gap presents an important challenge. This study examined potential strategies to support sustained engagement in dementia prevention activities. Participants and Setting: Members of senior citizens' clubs in Tottori Prefecture, Japan. Methods: This questionnaire survey collected data on basic demographics, frailty, and subjective cognitive decline (SCD). It also included questions on awareness of the Tottori Method Dementia Prevention Program, interest in experiencing the program if an instructor was dispatched, and the feasibility of engaging in the program through internet-based delivery or printed materials. Results: A total of 9,506 respondents were included in the analysis. Awareness of the dementia prevention program was 11.9%. Overall, 50.4% of the respondents registered a desire to try the program if an instructor was dispatched. The highest proportion of respondents (50.5%) reported willingness to engage in the program if materials summarizing activities that could be completed in approximately 10 min were provided. However, both frailty and SCD were associated with a lower interest in these dementia prevention activities (adjusted odd ratio [95% confidence interval] = 0.77 [0.67-0.89] and 0.86 [0.79-0.95], respectively). Conclusions: To promote sustained engagement in dementia prevention activities, opportunities to experience the program and activities that can be completed in a short time should be availed. However, disseminating research findings to the public remains challenging, and individuals at a higher risk of health problems may be less interested in dementia prevention. Proactive outreach strategies targeting high-risk individuals may be necessary to effectively disseminate the information.

We evaluated 2024/25 KP.2 vaccine effectiveness (VE) against COVID-19 hospitalization among adults >60 years old eligible for publicly-funded vaccination during fall and/or spring campaigns in the province of Quebec, Canada. We included Quebec residents tested for COVID-19-compatible symptoms in an acute-care hospital between October 13, 2024 (epi-week 2024-42) and August 23, 2025 (2025-34), linking vaccine, hospital, chronic diseases and laboratory administrative records to assess VE through test-negative design. We compared the odds of being COVID-19 test-positive versus test-negative among vaccinated versus non-vaccinated participants, adjusting for sex, age, comorbidities, place of residence, and epidemiological week. Overall, 49,949 (43%) participants were vaccinated. Over an analysis period spanning up to ten months, including median time since vaccination of 16 weeks (interquartile range 9-24 weeks), VE was 34% overall, declining from 43% <8 weeks to negligible by the 32nd week post-vaccination. Findings confirm meaningful but short-lived COVID-19 vaccine protection against hospitalization in older adults.