Journal of the American Geriatrics Society

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.

BackgroundSarcopenia is associated with increased fall risk, but its graded relationship with severity and age-specific patterns warrants further investigation in middle-aged and older adults. ObjectiveTo investigate the association between sarcopenia severity and fall risk among adults aged [≥]45 years and provide evidence for early intervention. MethodsUtilizing data from the China Health and Retirement Longitudinal Study (CHARLS) database (baseline 2011 to follow-up 2020), 9,608 participants without sarcopenia at baseline were included. Binary logistic regression analyses (univariate, multivariate, and interaction analyses) were employed to assess the association between sarcopenia severity and fall risk. The nonlinear effect of age was examined using restricted cubic splines (RCS curves). ResultsThe overall fall incidence rate among participants with sarcopenia was 18.88% (1,814/9,608). Fall incidence exhibited a graded increase with sarcopenia severity: non-sarcopenia group: 16.89% (1,108/6,560), possible sarcopenia group: 21.54% (439/2,038), confirmed sarcopenia group: 26.11% (217/831), and severe sarcopenia group: 27.93% (50/179). Multivariate logistic regression revealed a graded increase in fall risk with sarcopenia severity: possible sarcopenia (OR=1.28,CI[1.13-1.45]), confirmed sarcopenia (OR=1.36,CI[1.14-1.63]), and severe sarcopenia (OR=1.44,CI[1.02-2.03]). RCS curves identified a biphasic risk pattern: a modest rise between ages 45-60 and a steep increase after age 70, with 70 years as the inflection point. The subgroup analysis revealed that fall risk was significantly elevated in individuals with sarcopenia who were male, or who had a history of smoking, alcohol consumption, stroke, arthritis, or pain. Key interactions included a 2.96-fold risk in those aged 45-60 with severe sarcopenia (OR=2.96,[1.24-7.06]) and a 4.46-fold risk in those with confirmed sarcopenia and stroke (OR=4.46,[1.45-13.68]). ConclusionSarcopenia is an independent risk factor for falls, with risk increasing in a severity-dependent graded manner. Early identification of high-risk individuals and implementation of graded interventions are crucial.

BackgroundThere is growing consensus regarding the multidimensional nature of frailty and the need for comprehensive approaches to its assessment. However, existing assessment instruments have shown limited validity evidence or failed to adequately cover all the proposed theoretical dimensions of frailty. To address this gap, we recently developed the preliminary items of the Multidimensional Frailty Scale (MFS), a new instrument aimed to assess physical, cognitive, affective, social, and environmental frailty in older adults. This study sought to determine the final item set and to evaluate the psychometric properties of the final version. MethodsWe conducted a cross-sectional observational study with 283 individuals aged 65- 98 years. Participants completed the preliminary 51-item version of the MFS, the Tilburg Frailty Indicator (TFI), and a sociodemographic questionnaire. Item selection was guided by corrected item-dimension correlations, standardized factor loadings and content validity considerations. We examined dimensionality using confirmatory factor analysis comparing a unidimensional model and a five-factor second-order model, assessed internal consistency with Cronbachs alpha, and evaluated convergent validity through Spearman correlations between analogous dimensions of the MFS and the TFI. ResultsItem analysis yielded a final 29-item version of the MFS. The five-factor second-order model demonstrated excellent fit to the data, whereas the unidimensional model showed poor fit. Internal consistency was high for all dimensions and for the total scale. Convergent validity was supported by moderate-to-large correlations between corresponding MFS and TFI dimensions. ConclusionsThe MFS demonstrates robust psychometric properties and provides a brief yet comprehensive instrument to assess multidimensional frailty in older adults. Its hierarchical structure allows both global and domain-specific assessment, supporting more precise identification of frailty profiles. The ease of administration facilitates its use in research and clinical practice. Further validation in diverse linguistic and cultural contexts may enhance its applicability and support cross-national comparative research on multidimensional frailty.

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 [≥]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

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

BackgroundFalls among older adults are a leading cause of fractures, loss of independence, and need for long-term care. Community salons in Japan promote social participation and health activities among older adults. Hydrogen-rich water is widely used as a health product, but evidence in community settings remains limited. MethodsWe conducted a prospective observational study among 48 community-dwelling older adults attending community salons in Hiroshima City, Japan. Hydrogen-rich water was offered by the salon operators as part of routine activities; the research team did not assign participants to consume it. Participants were categorized at baseline according to their usual hydrogen-rich water consumption at the salons (consumers vs non-consumers) and followed for six months. The primary outcome was the 30-second chair stand test (CS-30). Secondary outcomes included the Timed Up and Go test (TUG), usual gait speed, one-leg stance time, and grip strength. Within-group changes and between-group differences in change scores were compared. ResultsAll 48 participants completed follow-up, and no serious adverse events were reported during the study period. The consumers group showed a greater improvement in CS-30 over six months (baseline 12.96 (SD 3.21) to follow-up 14.52 (SD 3.59); change 1.57 (SD 2.41)) compared with the non-consumers group (12.52 (SD 3.00) to 12.22 (SD 3.54); change -0.30 (SD 1.55)), with a significant between-group difference in change scores (p=0.003). The consumers group also showed a greater increase in usual gait speed (0.91 (SD 0.24) to 0.98 (SD 0.26); change 0.07 (SD 0.08)) than the non-consumers group (0.94 (SD 0.24) to 0.97 (SD 0.22); change 0.03 (SD 0.05); p=0.008). No significant between-group differences were observed for TUG (p=0.57), one-leg stance time (p=0.13), or grip strength (p=0.10). ConclusionIn community-dwelling older adults participating in community salons, routine hydrogen-rich water consumption was associated with improved lower extremity function as measured by CS-30 and gait speed. Because exposure was not randomized, residual confounding cannot be excluded, and causal inference is limited. Larger studies with stronger designs are warranted.

BackgroundBody composition strongly influences clinical outcomes in older adults, yet body mass index (BMI) lacks discriminatory power, and standard tools such as bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry are not routinely accessible. Deep learning enables scalable, opportunistic assessment of body composition from chest radiographs (CXRs), one of the most widely available imaging modalities. Methods and FindingsUsing the Inception-V3 architecture, we developed a deep-learning model using 107,568 paired CXR and BIA records (2016-2018). The model was temporally validated on a separate dataset of 77,655 records (2014-2015). Our model predicted skeletal muscle mass (SMM) and fat mass (FM) with high accuracy (SMM: Pearson r = 0.967, MAE 1.40 kg; FM: r = 0.924, MAE 1.61 kg). In a cohort of 5,932 older adults (aged [≥]65years), a 1-SD increase in CXR-predicted skeletal muscle index (SMI) was associated with a significant reduction in 10-year all-cause mortality (Hazard Ratio [HR] 0.65 [95% CI 0.58-0.73] for men; 0.80 [0.67-0.97] for women). In an external validation of 925 geriatric clinic patients, predicted SMI also showed comparable associations with geriatric parameters, including lower odds of sarcopenia (per 1 SD increase: 0.29 [0.22-0.38] for men; 0.25 [0.18-0.34] for women) and frailty (0.62 [0.48-0.78] for men; 1.00 [0.81-1.23] for women). These associations were more robust than those of BMI. Key limitations include the retrospective, single-center design and the use of a relatively healthy screening population. ConclusionA deep learning model applied to routine CXRs enables accurate estimation of skeletal muscle and fat mass, demonstrating prognostic and functional relevance comparable to BIA measurements. This approach may serve as a practical, low-cost tool for risk stratification and long-term care planning, particularly in older adults.

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

ObjectivesTo develop a simple risk prediction model for cognitive decline in a Chinese older adult cohort, and to evaluate its performance and transportability through temporal validation and external validation in a Japanese older adult cohort. MethodsThe prediction model was developed using a derivation cohort of 5,985 cognitively normal older adults from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). A comparison of seven machine learning algorithms was conducted, and the standard Cox Proportional Hazards (CoxPH) model was selected based on its optimal balance of performance and parsimony. The final model was then validated on a temporal cohort (CHARLS 2015-2018, n=1,333) and an external cohort (Japanese Study of Aging and Retirement [JSTAR] 2007-2009, n=2,798). A comprehensive preprocessing pipeline, including Iterative Imputation for high-missingness predictor variables and One-Hot Encoding for categorical variables, was developed on the training data and applied to all cohorts. Model performance was assessed via discrimination, calibration, risk stratification and clinical utility. ResultsIn temporal validation, the model demonstrated strong performance with an AUC of 0.72 and reliable calibration (Slope = 1.02). In the external JSTAR cohort, the model maintained high discriminative power (AUC = 0.68), which was even superior to the development set (AUC = 0.62). However, a notable calibration shift was observed (Slope = 1.54), indicating a systematic underestimation of absolute risk in the low-prevalence Japanese population. While decision curve analysis (DCA) showed substantial net benefit in the temporal cohort, its utility in the external cohort was most effective within a narrow threshold range near the population prevalence. Sensitivity analyses confirmed that the models risk-ranking ability remained robust across 2-year and 4-year horizons. ConclusionOur 6-predictor model shows robust risk-ranking consistency across cohorts, but absolute risk estimates are sensitive to population and temporal differences. While effective for identifying high-risk individuals, local recalibration is essential for accurate clinical prognosis in new settings.

ImportanceFrailty is a multisystem syndrome that reflects age-related physiological decline, underscoring the need for more biologically informed risk stratification within frailty assessments. Frailty and heart stress (HS) are individually associated with increased mortality risk, but their combined effects remain practically unexplored. ObjectiveTo evaluate whether the combined exposure to frailty and HS is associated with an increased risk of mortality. Design, Setting, and ParticipantsThis prospective cohort study used data from the US National Health and Nutrition Examination Survey (NHANES) and the Health and Retirement Study (HRS). Participants with complete data on frailty and HS were included. Analyses was performed between May 2025 and October 2025. ExposureFrailty was assessed using three frailty indices (FI) based on self-reported items (FI-Self-report), blood biomarkers (FI-Lab), and their combination (FI-Combined). HS was defined by age-adjusted elevation in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Participants were estimate into four groups according to baseline frailty and HS status. Main Outcomes and MeasuresThe primary outcome was all-cause mortality. Cox proportional hazard models were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsA total of 12,252 participants from NHANES (mean age 49.91 years, 52.18% female), and 9,488 participants from HRS (mean age 69.16 years, 58.97% female) were included. Compared with those having neither frailty nor HS, participants with frailty and/or HS showed significantly elevated mortality risk in both cohorts, with HRs ranging from 1.81 to 5.54. The highest mortality risk was observed in participant with both frailty and HS, the HRs were 3.58 (95% CI: 3.20-4.01) for FI Self Report, 3.43 (95% CI: 3.04-3.86) for FI Lab, and 4.15 (95% CI: 3.70-4.67) for FI Combined in NHANES; the corresponding HRs were 5.02 (95% CI: 4.38-5.76), 4.73 (95% CI: 4.13-5.41), and 5.54 (95% CI: 4.84-6.35) in HRS, respectively. Conclusions and RelevanceCo-occurrence of frailty and HS is common, and jointly associated with increased mortality risk in the general population. These findings support integrating HS into frailty assessments to improve mortality risk stratification and guide targeted interventions. Key PointsQuestion: Is the combination of frailty and heart stress (HS) associated with increased mortality risk? Findings: In this prospective cohort study including 12,252 participants from the US National Health and Nutrition Examination Survey (NHANES) and 9,488 participants from the Health and Retirement Study (HRS), participants with frailty and/or HS exhibited higher risk of all-cause mortality. The greatest mortality risk was found among participant with both frailty and HS. Meaning: These findings indicate that co-occurrence of frailty and HS is associated with increased mortality risk, supporting integration of HS into frailty assessment for risk stratification and intervention.

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

The Montreal Cognitive Assessment (MoCA) is widely used to screen for cognitive impairment, yet commonly applied cutoff scores have been found to perform poorly among US Latinos. Prior studies relied on small samples, combining persons with mild cognitive impairment (MCI) and dementia into a single group, or failing to account for multiple intersecting demographic factors. We identified optimal MoCA cutoffs for MCI and dementia among US Latinos while addressing these limitations. We analyzed cross-sectional data from the National Alzheimers Coordinating Center Unified Data Set. Participants included English- and Spanish-speaking Latinos who completed testing in their primary language. Research diagnostic groups consisted of cognitively unimpaired (CU), MCI, and dementia. Groups were further stratified by testing language, age, and level of education. Diagnostic accuracy and receiver operating characteristic (ROC) analyses were performed. The Youden Index was used to determine the optimal cutoff score. Of the 1,673 participants in the total sample, 46% completed the MoCA in Spanish and 54% in English, 54% were CU, and 28% had MCI and 19% had dementia. Area under the curve (AUC) values for CU vs. MCI were 0.70 for Spanish-tested participants and 0.79 for English-tested participants, while values for MCI vs. dementia were 0.85 and 0.89 for the Spanish and English tested participants, respectively. Overall AUC values were 0.76 for CU vs. MCI and 0.86 for mild cognitive impairment vs. dementia. Optimal cutoffs were consistently found to be lower among participants tested in Spanish, those older than age 75, and participants with the fewest years of education, with some optimal cutoffs shown to be substantially lower than the traditionally used standard cutoff. These findings provide cutoffs that better reflect differences amongst language and demographic groups. We also provide a scoring calculator for clinical and research use.

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

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

The aim of this study was to investigate the effects of cognitive dual-tasking on low-frequency oscillations during quiet standing in older adults. Thirty-two older adults (age 71{+/-}8 yrs) were categorized into high- and low-risk fall groups. Both groups performed three trials each of the following tasks: 1) quiet standing with eyes open - on a force plate; 2) quiet standing with eyes open and verbal memory encoding task - on a force plate; and 3) quiet sitting with eyes open and verbal memory encoding task - not on a force plate. We found that: A) older adults at high fall risk exhibit greater postural sway when compared with older adults at low fall risk, B) most of the absolute and normalized wavelet power from 0-4 Hz is concentrated within the 0-1 Hz frequency band across all directions, and C) the absolute change in wavelet power in the 0-1 Hz band from single to dual-task is associated with increased total COP sway displacement irrespective of fall risk group. Based on these findings, it is concluded that nonlinear postural sway measures provide valuable insights into age-associated changes in fall risk and dual-task performance. Focusing on low-frequency oscillations, particularly in the 0-1 Hz band, could enable the earlier identification of individuals at high risk of falls and a better understanding of how the dual-tasking paradigm challenges the aging population.

BackgroundAnticoagulants are often less frequently prescribed in elderly patients with atrial fibrillation (AF) because of concerns regarding high bleeding risk, despite their increased susceptibility to embolic stroke and systemic embolization. This study evaluated the impact of the Clinical Frailty Scale (CFS) on clinical outcomes and decision-making for prescribing antithrombotic therapy following left atrial appendage closure (LAAC) in a large contemporary registry. MethodsThe OCEAN-LAAC registry included 1,409 patients who underwent LAAC. Outcomes and antithrombotic prescriptions after the procedure were compared between groups stratified by CFS into 1-3 and 4-8. ResultsPatients with CFS 4-8 were more likely to have a history of stroke and demonstrated lower serum albumin and hemoglobin levels, consistent with advanced frailty. In multivariate analysis, CFS 4-8 was independently associated with higher all-cause mortality at one year compared with CFS 1-3 (adjusted hazard ratio 1.89; 95% confidence interval 1.05-3.41). By one year, patients with CFS 4-8 more frequently discontinued antithrombotic therapy, without significant differences in ischemic stroke or device-related thrombotic events. Notably, major bleeding was more common in the CFS 4-8 group, reflecting their advanced clinical vulnerability. ConclusionGreater frailty, as assessed by CFS, was independently associated with increased all-cause mortality following LAAC. Although frailty influenced patterns of antithrombotic therapy in this real-world registry, thrombotic events remained comparable between CFS groups, supporting the feasibility of individualized, frailty-guided post-LAAC management. These findings underscore the importance of incorporating frailty assessment into multidisciplinary Brain-Heart team decision-making.

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.

Gait variability is a critical functional indicator of dynamic balance and neurocognitive decline in health. Its translation into clinical practice is, however, challenged by a lack of age-related normative trajectories and reference values under real-world ecological settings. Furthermore, the conventional metrics used to estimate gait variability (Coefficient of Variation, CV; Standard Deviation, SD) have a fundamental methodological flaw: the inherent sensitivity of conventional metrics to the statistical outliers and environmental noise in real-world walking. In this study, we mitigate this factor by applying a robust statistical framework to quantify gait variability. Analysing a large-scale cohort of community-dwelling older adults (n=2,193), we first demonstrate that free-living gait data follows a heavy-tailed distribution, necessitating the use of robust estimators like the Robust Coefficient of Variation (RCV-MAD) and Median Absolute Deviation (MAD). Leveraging these metrics, we established the normative trajectory and reference values of real-world gait variability across the ageing lifespan, revealing a distinct, age-dependent increase in spatio-temporal fluctuations, indicating a decline in rhythmicity and steadiness with age. We further demonstrated the clinical utility of these robust metrics: RCV-MAD consistently yielded larger effect sizes than conventional CV in discriminating between fallers and non-fallers across all gait parameters. Furthermore, we illustrate the potential of long-term unsupervised monitoring to capture intrinsic variability during real-world walking. Validated for consistency and reliability, this robust framework provides the necessary ecological validity to transform gait variability into a standardised, rapid clinical metric for assessing functional decline at an early timepoint.

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