Journal of the American Geriatrics Society

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.

ObjectivesTo evaluate rates of treatment for depression and identify resident- and facility-level predictors of pharmacotherapy among long-term care (LTC) residents in the United States. DesignRetrospective, observational study. Setting and ParticipantsElectronic health record data from 1,675,873 LTC residents in the PointClickCare Life Sciences database (January-April 2025) were reviewed and 358,425 skilled nursing facility residents with a documented depression diagnosis were identified. MethodsResidents were classified as treated/untreated based on having a medication order for pharmacological depression treatment within medication classes recommended by the American Psychological Association. Descriptive analyses incorporated demographic and clinical characteristics, and multivariable logistic regression estimated odds of treatment. ResultsOverall, 81.7% of residents diagnosed with depression had [≥]1 pharmacological depression treatment order. Selective serotonin reuptake inhibitors (59.8%) and miscellaneous antidepressants (42.3%) were the most frequently used classes. Treatment rates were similar across depression diagnoses. Higher odds of receiving treatment were observed among residents also diagnosed with vascular dementia and those with hyperlipidemia medication orders. Lower odds were noted among residents who were Black or African American, had diabetes or hyperlipidemia diagnoses, or resided in facilities located in areas with poor socioeconomic status. Conclusions and ImplicationsMost residents with depression had at least one recommended pharmacologic therapy, although important disparities remain. Racial differences, comorbid conditions, and facility context continue to influence treatment access. These findings support the need for improved screening practices, greater attention to equity in prescribing, and strengthened clinical resources in socially vulnerable settings to enhance the quality of depression care in LTC facilities. Brief SummaryDepression is common in long-term care (LTC) and is associated with poor functional and clinical outcomes, however recent treatment patterns are not well understood. Using electronic health record data from 1,675,873 U.S. LTC residents between January and April 2025, 358,425 skilled nursing facility residents were identified with a documented depression diagnosis. The use of antidepressant medication was assessed based on medication order history and was aligned with American Psychological Association recommendations. Overall, 81.7% had at least one pharmacologic treatment order for depression; selective serotonin reuptake inhibitors (59.8%) and miscellaneous antidepressants (42.3%) were most frequently used. After adjusting for covariates, lower odds of treatment were observed among Black or African American residents and among residents in facilities located in more socioeconomically vulnerable areas. These findings highlight persistent inequities in depression pharmacotherapy in LTC and support efforts to strengthen depression assessment and ensure equitable access to evidence-informed treatment across facilities.

Background: Prediabetes is highly prevalent in older adults and is characterized by heterogeneous clinical trajectories, including regression to normoglycemia and progression to diabetes. While prediabetes has been associated with impaired physical function and frailty, the longitudinal impact of both a single diagnosis and dynamic glycemic transitions on functional outcomes remains unclear. We aimed to evaluate associations between baseline prediabetes and glycemic transitions over time with trajectories of functional capacity and frailty in older adults. Methods: We conducted a pooled analysis of harmonized data from five nationally representative longitudinal aging cohorts (MHAS, HRS, CHARLS, ELSA, CRELES) within the Gateway to Global Aging Data, including adults aged [≥]50 years with [≥]1 HbA1c measurements. Prediabetes was defined per ADA criteria (HbA1c 5.7-6.4%). Functional outcomes included activities of daily living (ADL), instrumental ADL (IADL), and frailty assessed using Fried phenotype, FRAIL scale, and a deficit-accumulation Frailty Index (FI). Mixed-effects Poisson models estimated incidence rate ratios (IRRs) for baseline prediabetes, while generalized estimating equations assessed time-varying glycemic status and transition trajectories. Models were adjusted for age, sex, cohort, and time-varying covariates, with sensitivity analyses including BMI, smoking, and alcohol intake. Findings: Among 18,571 participants (median follow-up 13.6 years), baseline prediabetes was associated with increased progression of functional deficits and frailty compared with normoglycemia, including higher FI values and accelerated FI progression. Prediabetes was associated with higher incidence of ADL, IADL, and multimorbidity deficits from early follow-up, although time-dependent changes in incidence rates were not significant. In time-varying analyses (n=7,840), both prediabetes and diabetes were associated with higher incidence of functional deficits compared with normoglycemia, with diabetes showing the strongest effects across all outcomes. Diabetes was associated with greater FI burden and accelerated progression, whereas prediabetes showed a smaller increase, with attenuation over time. Among individuals with baseline prediabetes, regression to normoglycemia occurred in 20.8% and was associated with increased incidence of ADL and frailty deficits. In contrast, progression to diabetes occurred in 24.3%, and was associated with lower risk of incident ADL and Fried frailty deficits compared to stable prediabetes. Interpretation: Prediabetes is associated with increased risk of functional decline, frailty, and deficit accumulation in older adults, independent of progression to diabetes. Regression to normoglycemia was associated with higher risk of functional deterioration. These findings suggest that prediabetes reflects a state of metabolic vulnerability linked to biological aging rather than solely a precursor to diabetes and highlights a need to reframe its clinical significance in older populations. Funding: This research was supported by Instituto Nacional de Geriatria in Mexico. Keywords: Prediabetes; Glycemic transitions; Frailty; Functional decline; Aging; Multimorbidity

Objectives: Cardiovascular disease (CVD) is a leading cause of mortality and disability in older populations. This study aimed to identify CVD risk factors in community-dwelling older adults and to examine whether frailty-related factors (sarcopenia and nutritional status) interact with chronic kidney disease (CKD). Methods: This cross-sectional study included 307 community-dwelling Japanese adults aged [&ge;]65 years between September 2024 and March 2025. CVD history was assessed based on self-reported physician diagnoses obtained through a structured questionnaire. Lifestyle-related factors included hypertension, diabetes, dyslipidemia, and body mass index (BMI). Frailty-related factors included sarcopenia (Asian Working Group for Sarcopenia 2019 criteria), nutritional status (Mini Nutritional Assessment-Short Form), and physical activity (International Physical Activity Questionnaire-Short Form). CKD was defined using the estimated glomerular filtration rate (eGFR): non-CKD ([&ge;]60 mL/min/1.73 m2) and CKD (<60 mL/min/1.73 m2). Multivariable logistic regression identified independent correlates of CVD, and interactions between CKD and frailty-related factors were tested. Results: The prevalence of CVD was 17.9%. Independent correlates included CKD (aOR 5.0), hypertension (aOR 4.0), male sex (aOR 3.1), undernutrition (aOR 2.7), sarcopenia (aOR 2.7), and low physical activity (aOR 2.5). No significant interactions were observed between CKD and sarcopenia (p = 0.70) or nutritional status (p = 0.40). Conclusions: CKD, sarcopenia, undernutrition, and low physical activity were independently associated with CVD, with no interaction between CKD and frailty factors. These findings suggest that integrated management addressing both renal function and frailty-related factors may be important for CVD prevention in older adults.

BackgroundOlder 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. MethodsFor 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. ResultsAll 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. ConclusionsFor 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.

Background: Despite the growing global burden of multimorbidity, the patterns of disease combinations, have not been extensively categorized. We aimed to explore the predictors, health consequences, and patterns of discordant and concordant multimorbidity. Methods: We used the 2018 China Health and Retirement Longitudinal Study (CHARLS), a representative database of adults aged >45 years from China. We conducted logistic regression analyses to assess the likelihood of having discordant (conditions from different disease systems) versus concordant (only cardiometabolic, or only respiratory diseases) multimorbidity, and to compare the health status and healthcare utilization between patients with discordant and concordant multimorbidity. Latent class analysis (LCA) was applied to both the entire sample and to patients with discordant multimorbidity to identify clusters of disease combinations. Results: The sample included 1668 patients with concordant (mainly cardiometabolic), and 7306 patients with discordant, multimorbidity. Female patients, patients living in rural settings, former and current smokers, and patients engaging in high-intensity physical activity, were more likely to have discordant instead of concordant multimorbidity. Depression, limitations in daily activities, poor self-reported health, and frequent healthcare use were more common in patients with discordant than concordant multimorbidity. The LCA identified five clusters when all multimorbid patients were included (cardiometabolic, arthritis-digestive, respiratory, multisystem, and arthritis-hypertension classes), and four clusters when restricted to discordant multimorbidity (digestive, arthritis-cardiometabolic, respiratory, and multisystem classes). Conclusion: Discordant multimorbidity is associated with poorer health and increased use of healthcare. Cardiometabolic diseases, arthritis, and digestive diseases have a central role in defining disease patterns.

BackgroundThe one-year SINEMA trial demonstrated improved blood pressure (BP) control and reduced mortality up to 72 months after the intervention. This article aims to assess between-arm differences in mean annual cumulative BP and to explore whether the associations between cumulative BP and biofunctional outcomes differed by trial arm. MethodsPost-hoc secondary analysis of the SINEMA cluster-randomized trial, which recruited 1299 adults with stroke from 50 rural villages in Hebei, China, between 2017 and 2018. The 12-month intervention was followed by observational assessments at 72 and 84 months post-baseline. BP was measured during each face-to-face follow-up, assessed by blinded assessors at baseline, 12, 72, and 84 months. Mean annual cumulative systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) were calculated. Biofunctional outcomes included health-related quality of life, modified Rankin Scale, activities of daily living, physical function, and cognition function. ResultsAmong 897 participants (mean age 62.7 years; 40.8% female) with complete data across all assessment, the intervention arm demonstrated significantly lower mean annual cumulative SBP (-2.2 mm Hg; 95% CI, -3.9 to -0.6), DBP (-1.6 mm Hg; 95% CI, -2.4 to -0.7), and MAP (-1.8 mm Hg; 95% CI, -2.8 to -0.8), not PP, compared with usual care. Significant associations between cumulative BP and biofunctional outcomes were observed in the control arm while not in the intervention arm. Interaction effects between trial arm and cumulative BP were significant for multiple outcomes, most prominently for cumulative SBP. ConclusionsThe one-year SINEMA intervention was associated with lower cumulative BP burden over 72-84 months but did not improve overall biofunctional outcomes. Secondary analyses revealed that the association between cumulative BP burden and biofunctional decline differed by intervention arm, suggesting cumulative BP exposure may be an important long-term risk indicator and the intervention may modify BP-outcome relationships through mechanisms requiring further investigation.

Background: LLMs enable patient-facing conversational agents, creating a pathway toward digital twins that capture older adults' lived experiences and behavioral responses across time. A central barrier is personality drift---inconsistent trait expression across repeated interactions---which undermines reliability of generated trajectories and intervention-response simulation in geriatric care. Objective: To develop ELDER-SIM, a multi-role elderly-care conversational platform for building personality-stable digital twin agents, and to propose a psychometric validation framework for quantifying personality consistency in LLM-based agents. Methods: ELDER-SIM was implemented via n8n workflow orchestration with local LLM inference (Ollama/vLLM), integrating (1) Big Five (OCEAN) trait specifications, (2) a Cognitive Conceptualization Diagram (CCD) grounded in Beck's CBT framework, and (3) a MySQL-based long-term memory module. Ablation studies across four conditions---Baseline, +Memory, +CCD, and +LoRA (fine-tuned on 19,717 instruction pairs from CHARLS)---were evaluated via Cronbach's $\alpha$, ICC, and role discrimination accuracy. Results: Personality measurement reliability was acceptable to excellent across conditions (Cronbach's : 0.70-0.94), with consistently high test-retest stability (ICC: 0.85- 2 0.96). Role discrimination improved stepwise from 83.3% (Baseline) to 88.9% (+Memory), 94.4% (+CCD), and 97.2% (+LoRA). CCD produced the largest gain in internal consistency (mean 0.702[-&gt;]0.892), while LoRA achieved the highest overall internal consistency ( 0.940) and ICC (0.958). Conclusions: ELDER-SIM provides a psychometrically validated approach for constructing personality-consistent elderly digital twin agents. Structured cognitive modeling and domain adaptation reduce personality drift, supporting reliable longitudinal simulation for elderly mental health care and reproducible in silico evaluation before clinical deployment.

Background: The role of biological age acceleration (BioAgeAccel) in the dynamic progression from single cardiovascular-kidney-metabolic disease (CKMD) to multimorbidity, and subsequently to dementia and mortality remains elusive. Methods: We conducted a longitudinal study with data of 433,911 UK Biobank participants. Cardiovascular-kidney-metabolic multimorbidity (CKMM) was defined as the coexistence of two or more CKMDs, including cardiovascular disease (CVD), stroke, type 2 diabetes (T2D), and chronic kidney disease. Biological aging was measured via PhenoAge and KDM-BA. Multistate models examined the association between BioAgeAccel and disease transitions, ranging from healthy to the first occurrence of CKMD (FCKMD), then progression to CKMM, dementia, and mortality. Restricted mean survival time estimated the disease transition time or life expectancy between states. Results: BioAgeAccel was significantly associated with increased risks across all disease transitions. Specifically, during CKMM progression, the hazard ratios (HRs) of the transition from healthy to FCKMD were 1.24 [95%CI 1.23-1.25] for PhenoAgeAccel and 1.16 [1.15-1.17] for KDM-BA-Accel. For subsequent transition to CKMM, the HRs were 1.20 [1.18-1.22] and 1.19 [1.17-1.21], respectively. In dementia-related transitions, PhenoAgeAccel showed the higher risk for CKMM to dementia (HR=1.13 [1.04-1.22]) than for the transition from healthy or from FCKMD to dementia. These associations were further moderated by age, physical activity, educational, and lifestyle factors. BioAgeAccel also accelerated disease progression and reduced life expectancy; for example, during CKMM progression, BioAgeAccel shortened the time between disease transitions by about 1.09 years from healthy to FCKMD, and an additional 1.75 years to CKMM. Regarding life expectancy, individuals with CKMM experienced an average reduction of about 1.36 years under PhenoAge, while those with dementia showed a decrease of about 0.77 years. Among individuals with CVD or T2D as the initial diagnosis, the impact of BioAgeAccel on progression to CKMM or dementia was stronger. Conclusions: BioAgeAccel exerts significant promotive role in the onset of CKMD and their subsequent progression to CKMM, dementia, and mortality, helping identify high-risk individuals. Implementing biological age assessments and health lifestyle interventions in middle-aged populations serves as an effective strategy for alleviating the burden of CKMDs and dementia.

Background Poor physical function has been associated with higher cardiovascular disease (CVD) risk. However, the association between physical function and atrial fibrillation (AF) remains understudied. The comprehensive investigation of the association between physical function and incident AF risk could highlight a novel target for AF prevention. Methods A total of 4,803 participants without diagnosed AF from the Atherosclerosis Risk in Communities (ARIC) Study cohort with physical function assessed in 2011-2013 were studied. Physical function was measured using Short Physical Performance Battery (SPPB), 4-meter walk time, and grip strength. Hospital discharge codes and death certificates were used to ascertain incident AF through 2022, and through 2020 for participants from Jackson. Cox regression was used to assess the association between physical function and incident AF risk, adjusting for multiple covariates. Z-score transformations were performed to identify the physical function measure most strongly associated with incident AF risk, and SPPB component analysis was performed to identify the most influential SPPB component. Results Mean age of the study participants was 75.1 {+/-} 5.0 years, with 41.2% being male participants and 22.2% being black participants. During a median follow-up of 9.2 years, there were 809 incident AF events. SPPB (HR: 0.93, 95% CI: 0.90-0.96, per 1-point increase) and grip strength (HR: 0.87, 95% CI: 0.78-0.96, per 10kg increase) were inversely associated with incident AF risk, while 4-meter walk time (HR: 1.08, 95% CI: 1.03-1.13, per 1-second increase) was positively associated with incident AF risk. SPPB had the strongest association with incident AF risk. Within SPPB, only the chair stand component was significantly associated with incident AF risk. Conclusions The findings suggest that better physical function is associated with reduced incident AF risk, with higher SPPB having the strongest association. Given the modifiable nature of physical function, these findings highlight a potential novel target for AF prevention in aging populations.

BackgroundAgeing is associated with reduced resilience to physiological stressors such as infection and surgery. This reduced resilience is believed to be underpinned by the hallmarks of ageing, the key biological mechanisms driving the aged phenotype. Geroprotectors are drugs that are proposed to slow down the ageing process and promote longevity and healthspan. Despite this, mechanistic studies in healthy older adults are lacking. Methods and AnalysisThis trial will test the hypothesis that geroprotectors targeted towards biological mechanisms associated with poor resilience can reverse these pathways within a three-week period. Three geroprotectors with a good safety profile in older adults and evidence of effect on the hallmarks of ageing will be administered to 60 (30 female; 30 male) adults 70+. Participants will be randomised to one of three arms (Metformin MR 1500mg, Fisetin 100mg or Spermidine 15mg). Participants will be extensively clinically characterised at baseline. Blood, abdominal adipose tissue and stool samples will be taken at baseline and following the three-week intervention. The primary research question will answer whether a three-week course of Metformin, Spermidine, or Fisetin reduce the number of senescent cells as measured by SA-{beta}-GAL in adipose biopsies in healthy older volunteers. Additionally, there will be assessment of the effect of the geroprotectors on other hallmarks of ageing, including autophagy, immunosenescence, chronic inflammation, dysregulated mTOR signalling, epigenetic age, DNA damage, dysregulated metabolism, stem cell exhaustion and microbial composition. Ethics and DisseminationEthical approval is in place (24/LO/0549). The main trial report and any sub-studies will be published in high impact peer-reviewed gerontology journals, presented at academic conferences and through a series of public engagement events. Participants enrolled in the study will be informed of the results by a written summary. Trial RegistrationREPROGRAM was registered with ISRCTN on 10/09/24. ISRCTN47919839. Available at https://www.isrctn.com/search?q=47919839. Trial Registration Data Set O_TBL View this table: org.highwire.dtl.DTLVardef@1db6074org.highwire.dtl.DTLVardef@1997837org.highwire.dtl.DTLVardef@a39a11org.highwire.dtl.DTLVardef@d7e6eforg.highwire.dtl.DTLVardef@7a5b7f_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1C_FLOATNO O_TABLECAPTIONTrial Registration Data Set C_TABLECAPTION C_TBL

BackgroundWe investigated frailty progression after severe infections in adults ([&ge;]65 years) in the US and England. MethodsWe conducted parallel matched cohort studies using: US Veterans Aging Cohort Study (VACS-National, 2008-2019; median age 74 years; 98% male); and English Clinical Practice Research Datalink (2006-2019; median age 76 years; 45% male). Adults hospitalised primarily for infection (i.e., severe infection) were matched in calendar date order to individuals without severe infection on age, sex, care site, and US only, plus race and ethnicity. We measured frailty using VACS Index 2{middle dot}0 (US) and Electronic Frailty Index (eFI; England). We estimated annual conditional mean frailty differences between adults with versus without severe infection using linear regression adjusting for baseline frailty, demographics, lifestyle factors, infection history, and US only, comorbidities. ResultsMean baseline frailty was higher in those with severe infection than those without (US: 57 v 48; England: 0{middle dot}17 v 0{middle dot}12). At Year 1, adjusted mean frailty was higher among adults with severe infections than those without (US: VACS Index +2{middle dot}0, 95% CI 1{middle dot}9-2{middle dot}0; England: eFI +0{middle dot}005, 95% CI 0{middle dot}005-0{middle dot}006). At Years 2-5, adjusted mean frailty remained higher after severe infection; however, compared to Year 1, differences were smaller in US, and larger in England. Effects varied by infection type (strongest for lower respiratory tract infections, meningoencephalitis (UK only), urinary tract infections, and sepsis). InterpretationIndividuals with severe infections had higher frailty at baseline and follow up than those without. Preventing both frailty and infections is important for improving health in older age. FundingWellcome Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed (inception to October 27, 2025), for published articles evaluating the association between infections and frailty, with no language restrictions. We used the search terms [(infection OR infectious) AND (frailty OR frail)]. We found fifteen observational studies investigating associations between individual infections (including: HIV, cytomegalovirus, SARS-CoV-2, acute respiratory infection, urinary tract infection, and influenza) and frailty in adults. Frailty measures varied: eight studies used Frieds phenotype index, six used versions of the cumulative deficit index (i.e., Edmonton Frail Scale, FRAIL-NH Scale, Hospital Frailty Risk Score, Clinical Frailty Score, Veterans Affairs Frailty Index, Vulnerable Elders Survey-13), and one study used the Timed Up and Go Test. Results from identified studies were mixed, with nearly half (7/15) reporting a positive association between the infection studied and frailty, and the remaining eight finding no evidence of association. In cross-sectional analyses, HIV, SARS-CoV-2, cytomegalovirus, and urinary tract infection, were each associated with higher mean frailty scores or frailty prevalence. In longitudinal analysis, hospitalisation for acute respiratory infection was followed by higher mean hospital frailty risk scores two years post-discharge. SARS-CoV-2 infection was associated with early onset (i.e., higher hazard) of frailty over three years follow-up. However, other studies found no association between HIV, SARS-CoV-2, acute respiratory infection and influenza, and frailty prevalence, incidence, or transition between frailty states. These mixed findings may reflect methodological differences between the studies, including variation in frailty measures, and study limitations. Frailty exists along a continuum of vulnerability, and progression after infection may be an important outcome, yet current evidence is scarce. It remains unclear whether severe infections or different types of infection, are associated with faster frailty deterioration. Similarly, it is uncertain whether post-infection frailty risk varies by pathogen (bacterial, viral, parasitic, fungal), infection type (sepsis, urinary tract infection, skin and soft tissue infection, meningitis/encephalitis, lower respiratory tract, gastroenteritis), or by age, sex, social deprivation, and pre-existing comorbidities. Added value of this studyOur study compared frailty progression over a five-year period between adults aged [&ge;]65 years with severe infection (hospitalisation primarily due to infection) versus comparators without severe infection. We found higher baseline frailty at severe infection onset than in matched comparators. We saw evidence of increased frailty progression over time in people following severe infections compared to those without, however, these differences were small. We also saw higher risk of worsening frailty progression in older adults and those with dementia. Further, worsening frailty progression varied by infection type (strongest for lower respiratory tract infections, meningoencephalitis (UK only), urinary tract infections, and sepsis). Implications of all the available evidenceOur findings underscore the importance of both frailty and infection prevention in improving health in older age. Additional studies are required to explore other wider life-course influences on frailty, to guide the development of comprehensive preventive strategies.

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.

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.

BackgroundVestibular complaints are common in older adults and are linked to imbalance and falls. Some older adults show impaired vestibular perception despite preserved peripheral-reflex ("vestibular agnosia"). Yet it remains unclear if vestibular agnosia is independently linked to imbalance and falls in otherwise healthy older adults. We therefore investigated the prevalence of vestibular agnosia in community-dwelling older adults, and examined its association to balance and prospective falls. MethodsVestibular perceptual thresholds were measured during yaw-plane rotational chair testing. Postural sway and instrumented Timed-Up-and-Go were assessed using wearable sensors, and falls were recorded prospectively over six-month. Vestibular agnosia was identified using K-means clustering. Multivariable regressions examined associations between perceptual thresholds and balance outcomes; logistic and negative binomial regressions evaluated associations with prospective falls. ResultsAmong 166 participants (75.4 years; 81.9% female), 18.7% were classified as having vestibular agnosia. These individuals had worse cognition and somatosensation. Elevated (i.e. worse) vestibular perceptual thresholds were independently associated with greater sway velocity when standing on foam with eyes-open (adjusted {beta}=0.002, p=0.03). Associations with other balance outcomes were attenuated after adjustment. Vestibular perceptual thresholds were not associated with prospective falls (odds of [&ge;]1 fall: adjusted OR=0.99, p=0.65; fall counts: adjusted IRR=1.02, p=0.35). ConclusionsApproximately one-fifth of healthy older adults exhibit vestibular agnosia. While elevated perceptual thresholds are independently associated with poorer balance, they did not predict falls. Vestibular perceptual testing provides complementary insight into age-related balance impairment, although its utility in fall-risk prediction requires further investigation. Key PointsO_LIApproximately one-fifth of healthy older adults had vestibular agnosia (impaired vestibular perception despite intact peripheral function) C_LIO_LIOlder adults with vestibular agnosia have poorer cognition, reduced lower limb somatosensation, and higher anxiety. C_LIO_LIHigher (i.e. worse) vestibular perceptual thresholds were independently associated with greater sway velocity when standing on foam (eyes open). C_LIO_LIHigher vestibular perceptual thresholds were only associated with slower TUG performance and greater eyes-closed foam sway in unadjusted models. C_LIO_LIVestibular perceptual thresholds did not predict prospective falls over 6 months. C_LI

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.

BackgroundAtrial fibrillation and flutter (AF/AFL) represent a major global public health challenge, contributing significantly to stroke, heart failure, and cardiovascular mortality. While previous studies have documented a rising AF/AFL burden, comprehensive comparisons of long-term trends and forecasts across regions--particularly benchmarking China against Southeast Asia, Europe, and global averages--remain limited. This study aims to quantify the AF/AFL burden across these regions from 1990 to 2021 and project trends to 2050. MethodsUsing data from the Global Burden of Disease Study 2021, we analysed the burden of AF/AFL from 1990 to 2021 in China, Southeast Asia, Europe, and globally. We examined incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Advanced analytical methods, including Joinpoint regression, age-period-cohort modelling, decomposition analysis, Frontier analysis and Bayesian forecasting were employed to assess trends, drivers, and projections to 2050. FindingFrom 1990 to 2021, China experienced the most rapid increase in age-standardized incidence rate (ASIR) globally (AAPC +0.16%), with incident cases rising to 916,180, accounting for 20.43% of the global total. In contrast, Europe saw a slight decline in ASIR, while the global ASIR remained stable. China also recorded the largest increase in age-standardized prevalence rate (ASPR), whereas Europes ASPR declined. Despite rising incidence, China achieved the sharpest reduction in age-standardized mortality rate (ASMR; AAPC -0.45%), while Southeast Asias ASMR increased (AAPC +0.76%), and Europe maintained the highest ASMR globally. Frontier analysis highlighted Chinas rapid efficiency improvements in mortality reduction relative to its SDI, outperforming several high-income European countries. Projections to 2050 suggest Chinas ASIR and ASPR will continue to rise, whereas Europes are forecast to decline. Southeast Asia faces persistently increasing mortality, and global aggregates mask significant regional heterogeneity. ConclusionAF/AFL burdens are increasingly driven by population aging and metabolic risks, with heterogeneous mortality trends reflecting regional disparities in healthcare access and prevention. China s success in reducing mortality despite rising incidence highlights the impact of improved anticoagulation and stroke prevention, yet unchecked prevalence growth signals future complications. Southeast Asia s rising mortality underscores urgent needs for equitable resource allocation, while Europes stagnant burden reflects challenges in aging populations. Globally, prioritising primordial prevention--such as metabolic risk control--alongside targeted screening and gender-specific interventions, is critical to mitigating AF/AFL-related morbidity and mortality. Future efforts should integrate digital health technologies and address structural barriers to optimize care efficiency worldwide. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSPrior to undertaking this analysis, we systematically reviewed the existing epidemiological literature on atrial fibrillation and atrial flutter (AF/AFL), with a particular emphasis on global and regional comparative studies. Our searches covered PubMed, Embase, Web of Science, the Cochrane Library, and the Global Burden of Disease (GBD) repository from January 1990 to December 2023, without language restrictions. Key terms included "atrial fibrillation," "atrial flutter," "global burden," "epidemiology," "trend," and "GBD." We included studies providing representative estimates of AF/AFL burden and excluded small-sample or non-age-standardized reports. Previous analyses indicated a rising global AF/AFL burden, largely due to population aging and improved detection. However, comprehensive assessments capturing temporal dynamics, risk drivers, and forecasting across major world regions--especially benchmarking China, Southeast Asia, and Europe against global patterns--remained limited. Most studies focused on isolated regions or short spans, lacking integrative multidimensional approaches such as age-period-cohort modeling, decomposition, or Bayesian forecasting. Added value of this studyThis study provides a comprehensive and comparative assessment of the atrial fibrillation and atrial flutter (AF/AFL) burden across China, Southeast Asia, Europe, and globally from 1990 to 2021, utilizing the latest GBD 2021 data and advanced statistical methodologies, including Joinpoint regression, age-period-cohort modeling, Bayesian forecasting, decomposition analysis, and data envelopment frontier analysis. Our analysis reveals significant regional disparities against a backdrop of global stability: while the global age-standardized incidence rate (ASIR) remained stable (52{middle dot}51 in 1990 vs. 52{middle dot}12 in 2021), China experienced the most rapid increase worldwide (ASIR rising from 42{middle dot}63 to 44{middle dot}92), with a substantial number of new cases (916,180), accounting for 20{middle dot}43% of the global total (4,484,926 cases). In contrast, Europe recorded a slight decline in ASIR. China also demonstrated the most pronounced increase in prevalence globally, while Europes age-standardized prevalence rate (ASPR) declined and the global rate remained largely unchanged. Notably, China achieved a significant reduction in mortality (age-standardized mortality rate [ASMR] declining from 4{middle dot}93 to 4{middle dot}33) despite rising incidence, sharply contrasting with Southeast Asia, where ASMR increased from 2{middle dot}94 to 4{middle dot}06 (estimated annual percentage change +1{middle dot}07%)--trends potentially associated with structural challenges in Southeast Asia--while Europe maintained the highest ASMR globally (5{middle dot}10 in 2021) despite interventions. We further identified key drivers: population growth and aging accounted for the majority of the case increase in China, consistent with global demographic trends, while metabolic risk factors accelerated this trend. Gender and age analyses revealed a global pattern of later-life predominance in women and earlier onset in middle-aged groups, particularly pronounced in China. Our projections to 2050 indicate a continued rise in ASIR and ASPR in China, reinforcing its significant and growing contribution to the global AF/AFL burden, whereas other regions face divergent challenges--Southeast Asia is projected to experience persistently increasing mortality pressure, while Europe must address persistently high disability-adjusted life year (DALY) rates, masking mortality gains in an aging population. Implications of all the available evidenceThe collective evidence from this study and previous research underscores that AF/AFL remains a critical and growing public health challenge worldwide, characterized by heterogeneous patterns across regions when viewed against the global aggregate. Chinas success in reducing mortality within a rising incidence environment highlights the potential of enhanced clinical management and stroke prevention, yet its unchecked prevalence growth--especially among younger cohorts--signals a looming surge in complications absent strengthened primary prevention, a concern mirrored in many developing economies. Southeast Asias rising mortality underscores urgent needs for improved access to anticoagulation and rhythm control, while Europes stagnant burden reflects challenges in managing an aging population efficiently. These findings advocate for regionally tailored strategies that align with global frameworks but address local disparities--integrating primordial prevention (e.g., metabolic risk control) with early detection, gender-specific treatment, and equitable resource allocation. Future research should prioritize mechanistic studies of AF/AFL subtypes, real-world intervention assessments, and the integration of digital health technologies for scalable screening and management, thereby informing coordinated global actions to mitigate the evolving burden of AF/AFL.

Biomarkers of aging, particularly DNA methylation-based clocks, have shown promise as tools to assess whether interventions may impact the rate of biological aging. Among possible interventions physical exercise has shown protective effects against many age-associated diseases, while time-restricted feeding (TRF), has shown metabolic benefits in preclinical models. The combined effect of exercise and TRF on aging biomarkers remains largely unexplored. In this 52-week four-armed, randomized, controlled trial (clinicaltrials.gov: NCT07207044) 240 healthy adults aged 65 and over will be allocated to four groups: combined cardio and strength training (EXE), TRF, combined EXE and TRF, or control. Participants will undergo assessments at baseline, 3, 6, and 12 months, with follow-ups at 2, 5, and 10 years. The primary outcome measure is DNA-methylation age with secondary measures including RNA-sequencing, metabolomics, inflammatory marker, microbiome analysis, cognitive and physical measures. By deeply phenotyping participants the Fasting And eXercise (FAXAge) study will provide novel insights into whether TRF, EXE, or a combination can slow or reverse biological aging in older adults.

BackgroundPrevious studies established handgrip strength (HGS) as a potential risk factor for cardiovascular diseases (CVD). However, existing studies focused exclusively on baseline HGS and neglected longitudinal changes in HGS during follow-up. Thus, our aim was to investigate the associations of transitions and dynamic burdens of HGS with incident CVD risk. MethodsWe analyzed data from the UK Biobank (UKB), the China Health and Retirement Longitudinal Study (CHARLS), the Survey of Health, Ageing and Retirement in Europe (SHARE), and the Korean Longitudinal Study of Ageing (KLOSA). We defined HGS transitions based on HGS at baseline and the first follow-up, and created three indicators to reflect HGS burdens. Cox models were applied to examine the association of HGS transitions and burdens with incident CVD risk. The predictive value of HGS indices was also evaluated. ResultsA total of 73,555 participants were retained, and 4,722 (6.4%) incident CVD cases were identified during follow-up. Transition analyses revealed that increased HGS during follow-up was associated with reduced CVD risk, whereas decreased HGS was associated with an elevated risk. Per standard deviation decrement in HGS slope, cumulative HGS and relative cumulative HGS led to a 19.8% (95%CI 1.5~41.5%), 44.0% (95%CI 10.8~87.2%) or 26.7% (95%CI 9.4~46.8%) elevated risk of CVD, respectively. These associations were independent of and more pronounced than HGS, with stronger effects observed in East Asian cohorts (CHARLS and KLOSA) compared to European cohorts (UKB and SHARE). Incorporating dynamic HGS metrics enhanced the predictive accuracy, with HGS burdens providing greater gains than HGS. For the optimal models, all HGS indices resulted in an increase of AUC up to 7.6% in Europeans and 5.9% in East Asians. ConclusionsHGS burdens outperformed in predicting cardiovascular health compared to single cross-sectional HGS itself, suggesting the clinical utility of longitudinal HGS monitoring in clinical and public health strategies for CVD prevention.

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.