Journal of the American Geriatrics Society

Objectives: To estimate hyperlipidemia medication order prevalence and associated variables in U.S. skilled nursing facility (SNF) residents. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 447,080 SNF residents with a hyperlipidemia diagnosis identified in PointClickCare's Life Sciences clinical database (January-April 2025) were reviewed. Methods: The presence and absence of medication orders for hyperlipidemia treatments recommended by the American Heart Association were assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 83.3% of residents diagnosed with hyperlipidemia had at least one hyperlipidemia medication order. Statins were ordered by 96.2% of active order residents, while other medication classes i.e., omega-3 fatty acids, cholesterol absorption inhibitors, fibrates were less common (<8%). Risk ratios (RRs) for medication orders ranged from 0.87-1.16. Factors most strongly associated with having an order included hypertension medication orders (RR=1.16), unspecified hyperlipidemia diagnosis (RR=1.10), and active diabetes medication orders (RR=1.09); female sex (RR=0.95) and private (0.94) or other (0.87) payer types were associated with a lower likelihood of having an order. Conclusions and Implications: Most residents with a hyperlipidemia diagnosis had an active relevant medication order, but use of non-statin therapies was rare. Differences in treatment patterns by sex and payer type, along with limited uptake of newer agents, warrant further investigation into prescribing practices and access within SNFs.

Objectives: To evaluate rates of pharmacological hypertension orders and identify resident- and facility-level predictors of pharmacologic care among skilled nursing facility (SNF) residents in the United States. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 1,285,062 long-term care residents in PointClickCare's Life Sciences database in facility on April 30, 2025 were reviewed, and 553,519 SNF residents with a documented hypertension diagnosis were identified. Methods: The presence and absence of medication orders for antihypertensive treatment recommended by the International Society of Hypertension was assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios (RRs) for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 87.7% of residents diagnosed with hypertension had at least one antihypertensive medication order. Calcium channel blockers (44.3%) and beta blockers (43.5%) were the most frequently used classes. RRs ranged from 0.91 to 1.09. Higher likelihoods of antihypertensive orders were observed among residents prescribed hyperlipidemia and diabetes medication (RR = 1.09 and 1.05, respectively), while lower likelihoods of treatment were observed for other payer types (RR = 0.91), diabetes diagnoses (RR = 0.95), and hyperlipidemia diagnoses (RR = 0.98). Conclusions and Implications: Most residents with hypertension had orders for recommended pharmacologic therapy, although important gaps and disparities remain. The predominance of certain medication classes and persistent differences by comorbidity and facility type underscore the need for targeted strategies to improve equitable prescribing and access to evidence-based hypertension management in SNF settings.

Background Delirium is common among hospitalized older adults on many clinical services and associated with poor outcomes. Given delirium's fluctuations, wearable devices are promising continuous monitors. While recruiting for a wearable electroencephalography (EEG) delirium study, we initially experienced low enrollment rates among older adults and patients on non-neurologic services. Our aim was to understand patient and community perspectives on inpatient, wearable research to adapt recruitment protocols and increase enrollment. Methods We approached patients admitted to an academic medical center to participate in an observational, wearable EEG delirium study and recorded reasons for enrolling or declining. To gain insight into recruitment protocols, we held a community panel with patients, family members, and caregivers. Recruitment protocols were refined in two phases: 1) personalizing the recruitment approach to emphasize symptoms that were personally relevant to individual patients and 2) sharing educational materials about the study in addition to delirium. We compared enrollment rates before and after these protocol adaptations. Results Initially, 18.5% of approached patients enrolled (68/367). Despite antecedent concerns that wearable devices would be the primary deterrent to participation, only a small proportion of people who did not participate did so because of wearable EEG (8.8%, 26/299). Community panel members (n=7) suggested that personal relevance and understanding of the clinical conditions being studied, such as delirium, would have a greater impact on decisions to participate than study procedures. Adapting recruitment protocols to highlight personally relevant delirium-related symptoms, such as sleep disturbance, significantly increased enrollment rates (30.1%, 58/188, p<0.001), including for patients over 65 years old (p<0.001) and patients on non-neurologic services (p<0.001). The addition of educational materials focused on clinical delirium did not further impact enrollment (p=0.61). Conclusions Recruitment of older, hospitalized patients for inpatient research can be challenging, but can be significantly improved by highlighting familiar symptoms of personal relevance.

Importance: The ASPREE randomized trial found no overall benefit of low-dose aspirin for disability-free survival among older adults. However, individual estimates in pre-specified subgroups indicated potential benefit among racial and ethnic minoritized participants in the United States (US). Objective: To evaluate whether the effect of low-dose aspirin vs placebo on disability-free survival differed across US Black and Hispanic ASPREE participants using individualized treatment-effect estimation. Design, Setting, and Participants: Post hoc clinical trial analysis of ASPREE, a randomized, double-blind, placebo-controlled clinical trial of daily low-dose aspirin vs placebo. This analysis included US ASPREE participants who self-identified as non-Hispanic Black or Hispanic, were aged 65 years or older, and had complete baseline predictor and outcome data. Interventions: Randomization to daily 100-mg aspirin or placebo. Main Outcomes and Measures: The primary outcome was loss of disability-free survival, defined as death, persistent physical disability, or dementia. Individualized treatment effects were estimated post hoc using a Random Survival Forest X-learner. Heterogeneity was evaluated on the relative scale with Cox proportional hazards models and on the absolute scale with 5-year risk differences. Results: Among 2411 US ASPREE participants, 1270 were included in the Black and Hispanic analytic cohort (897 non-Hispanic Black and 373 Hispanic participants; mean age, 71.8 years). Aspirin was associated with lower risk of disability-free survival loss compared with placebo (hazard ratio [HR], 0.65; 95% CI, 0.45-0.93). In model-derived tertiles, aspirin was associated with lower risk in the greatest predicted-benefit group (HR, 0.36; 95% CI, 0.19-0.71; 5-year absolute risk difference [ARD], -11.1 percentage points; 95% CI, -22.0 to -0.1) but not in the lowest predicted-benefit group (HR, 1.26; 95% CI, 0.70-2.27; ARD, +3.9 percentage points; 95% CI, -5.9 to 13.6). Conclusions and Relevance: In these analyses of US Black and Hispanic ASPREE participants, aspirin effects on disability-free survival appear to be heterogeneous, with benefit concentrated in a subset of participants. Because these findings are from post-hoc models, they should be externally validated before being incorporated into clinical decision-making. Trial Registration: ClinicalTrials.gov Identifier: NCT01038583; https://clinicaltrials.gov/study/NCT01038583

Background: Existing electronic frailty indices (eFI) are typically based on structured data and designed for older adults. We developed an eFI that integrates structured and unstructured electronic health records (EHRs) across adulthood and assessed its longitudinal trajectories and associations with adverse outcomes. Methods: We used longitudinal EHR data from 193629 individuals aged 35-103 in the Wellbeing Services County of Central Finland (2010-2023) and constructed a 53-item eFI including diagnosis codes, laboratory tests and items extracted from free-text clinical notes using deep-learning-based natural language processing. Associations with all-cause mortality, severe infections, fractures, and healthcare utilization were assessed using Cox and count models. Predictive performance was compared with Hospital Frailty Risk Score (HFRS) and Charlson Comorbidity Index (CCI). Findings: eFI trajectories accelerated notably from age 65 onwards. Using the eFI as a categorical variable, severe frailty was associated with higher risks of mortality (hazard ratio [HR] 7.31, 95% confidence interval [CI] 6.83-7.83), severe infections (HR 9.22, 95%CI 8.52-9.98), fractures (HR 2.75, 95%CI 2.52-3.01) and increased healthcare utilization (odds ratio [OR] 3.15, 95%CI 2.96-3.35) compared with non-frail. The risks were relatively greater in younger age groups and persisted when using the continuous eFI restricted to non-frail individuals. Across all outcomes, the eFI showed greater model discrimination than HFRS and CCI. Interpretation: An eFI using structured and unstructured EHR data improves risk stratification even in younger adults and at very low levels of frailty. Funding: Research Council of Finland, Instrumentarium Science Foundation, Sigrid Juselius Foundation and Samfundet Folkhalsan.

Background Falls are increasingly recognized as adverse events in coronary heart disease (CHD) patients, yet their prognostic implications remain incompletely understood. This study examined the independent associations of falls with mortality and major adverse cardiovascular events, and the roles of functional status and frailty in these relationships. Methods This retrospective cohort study enrolled 2,139 CHD patients with median follow-up of 36 months. Falls were ascertained via telephone interviews every 3 months. Primary outcomes included major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary outcomes comprised all-cause and cardiac mortality. Multivariable Cox models with stepwise adjustment for functional status indicators were constructed, with subgroup analyses stratified by frailty status. Results During follow-up, 171 patients (8.0%) experienced falls. Falls were associated with mortality in univariate analysis but not after adjusting for functional status, indicating mediation by functional decline. In contrast, falls remained independently associated with MACE (HR=1.73, 95%CI: 1.17-2.57, P=0.006) and MACCE (HR=1.67, 95%CI: 1.14-2.46, P=0.009) in fully adjusted models. Frailty significantly modified this association (P for interaction <0.001). Among robust patients, falls conferred substantially elevated risk (MACE: HR=4.08, 95%CI: 2.37-7.01; MACCE: HR=3.94, 95%CI: 2.30-6.76), whereas no significant association was observed in pre-frail or frail patients. Conclusions Falls independently predict long-term MACE and MACCE in CHD patients, with mortality effects mediated by functional status. Frailty significantly modifies the fall-cardiovascular event relationship--robust patients experiencing falls face substantially elevated cardiovascular risk and warrant comprehensive evaluation. These findings support integrating fall history into cardiovascular risk assessment and implementing frailty-stratified management.

Importance: Preclinical and human observational studies suggest that metformin may decrease age-related pathology, including frailty. Objective: Determine whether metformin reduces frailty progression and biological age in older adults with glucose intolerance, a population at increased risk of becoming frail. Design, Setting and Participants: Randomized, double-blind, placebo-controlled trial of metformin in 145 non-frail or pre-frail older adults. Participants (72 +/-5 years, 48% female, 94% White, 35% Hispanic) were randomized to metformin vs. placebo for two years. Main Outcomes and Measures: Effect on frailty was primarily determined using generalized estimating equations by change in the Fried frailty phenotype score (based on weight loss, exhaustion, physical activity, gait speed, and grip strength). Because metformin can cause significant weight loss, effects on the Fried score were assessed with and without the weight loss criterion. Frailty also was assessed by change in the frailty index (composite of 95 deficits). Biological age was estimated by DNA methylation-based epigenetic clocks in blood. Results: Metformin led to a non-linear response in the Fried score rate of change, with an upward trajectory in year 1 (0.72 +/-0.22 per year vs. placebo, p=0.0011) and stabilization in year 2 (-0.33 +/-0.17 per year vs. placebo, p=0.056). Metformin led to more weight loss than placebo (-5.7 +/-5.2 vs. -2.3 +/-5.4 kg, p=0.0002); thus, when assessing effect on Fried score without the weight loss criterion, no difference was observed, indicating that weight loss in year 1 accounted for the change in Fried score. Notably, metformin caused a steady improvement in the frailty index (-0.006 +/-0.0026 per year vs. placebo, p=0.0222) that persisted with covariates adjustment including body mass index. Metformin reduced biological age estimated by PC-Horvath2 (-0.40 +/-0.16 per year, p=0.014) and PC-Hannum (-0.33 +/-0.16 per year, p=0.047) clocks. Metformin was well tolerated. Conclusions and Relevance: Metformin halts the progression of the deficit accumulation frailty index and reduces biological age, suggesting potential benefit for extending healthspan. Trial Registration: ClinicalTrials.gov: NCT02570672.

Objectives: Physical and cognitive aging do not occur uniformly, yet associations between specific physical function and cognitive domains in sedentary older adults remain unclear. This exploratory cross-sectional study examined associations between multiple physical function domains and cognitive outcomes in sedentary, community-dwelling, cognitively unimpaired older adults. Methods: Fifty-eight older adults (70.7{+/-}4.7 years; 84.5% Female) completed handgrip strength, 30-second chair stand, timed up and go (TUG), brisk walk, and 6-minute walk (6MWT) assessment. Cognitive outcomes included global cognition using the Montreal Cognitive Assessment (MoCA), and working memory, episodic memory, attentional inhibition, and cognitive flexibility using the NIH Toolbox. Linear regression models adjusted for age, sex, education, body mass index, and brachial pulse pressure. False discovery rate (FDR) correction was applied. Results: Greater 6MWT distance was associated with better episodic memory performance after FDR correction ({beta}=0.49, pa=0.028). Additional inverse associations were observed between TUG performance and global cognition ({beta}=-0.34, pa=0.166) and attentional inhibition ({beta}=-0.32, pa=0.180), and between gait speed and global cognition ({beta}=-0.33, pa=0.166) and episodic memory performance ({beta}=-0.32, pa=0.166), however, these did not survive FDR correction. Handgrip strength and chair stand performance were not associated with cognitive outcomes. Conclusions: These exploratory findings suggest that locomotor-based functional tasks may demonstrate stronger cognitive associations than strength measures in sedentary, cognitively unimpaired older adults. Tasks involving sustained locomotion and adaptive movement may place greater cognitive-motor demands, potentially increasing sensitivity to subtle cognitive variation. Larger longitudinal and multimodal studies are needed to determine whether these associations reflect reliable differential patterns across physical and cognitive domains.

Background: The urinary sodium-to-potassium (Na/K) ratio is an integrated biomarker associated with cardiovascular risk. However, its association with deep white matter lesions (DWMLs), a manifestation of cerebral small vessel disease (CSVD), remains unclear. We investigated the associations of the urinary Na/K ratio and albuminuria with DWMLs. Methods: We conducted a cross-sectional study of 296 Japanese adults (mean age, 68.7 years). Brain magnetic resonance imaging was used to assess DWMLs using the Fazekas scale, and lesions were classified as absent (grade 0) or present (grades 1?3). The urinary Na/K ratio and albumin excretion were measured using 24-h urine collections. Multivariable logistic regression models examined the associations between urinary biomarkers and DWMLs. Results: DWMLs were present in 119 (40.2%) participants. A higher urinary Na/K ratio was independently associated with DWMLs (odds ratio per 1?standard deviation increase, 1.44; 95% confidence interval, 1.09?1.90; P=0.010). Participants in the highest quartile had greater odds of DWMLs than those in the lowest quartile (odds ratio, 2.48; 95% confidence interval, 1.16?5.29; P=0.019). Urinary potassium excretion was inversely associated with DWMLs, whereas urinary sodium excretion alone showed no significant association. Findings were consistent across sensitivity and subgroup analyses. Conclusions: A higher 24-h urinary Na/K ratio was independently associated with DWMLs in older adults. This association appeared to be driven primarily by lower urinary potassium excretion rather than higher sodium excretion alone. The urinary Na/K ratio may serve as a simple, noninvasive marker of CSVD.

Abstract Background: Disability prediction in elderly with cardiometabolic multimorbidity (CMM) is limited. We developed a dynamic nomogram and addressed three questions: predictive value of routine blood markers, depression vs. physical function, and plateau in CMM count.Methods: Using CHARLS data (46 predictors), disability defined as ADL/IADL impairment or self-report. LASSO and logistic regression built the nomogram, with mediation, RCS, trend tests, machine learning, and SHAP.Results: Six predictors (depression, cognition, stroke, CMM number, age, falls) formed a good-performing nomogram (https://xjbsashjtdx.shinyapps.io/DynamicNomogram/). Left-hand grip strength mediated 12.3% of strokes effect. Cognition showed an inverted U-shape (inflection point=12.043). CMM count plateaued after 3 diseases. Depression outranked grip strength and walking speed. SHAP identified HbA1c, creatinine, uric acid, hematocrit, fasting glucose, TyG, and CVAI as risk markers.Conclusions: The nomogram enables personalized risk stratification. Routine blood markers predict disability, depression dominates over physical function, and the CMM-disability relationship plateaus at CMM[&ge;]3.

Background Whether adiposity is protective against or detrimental to skeletal muscle health in older adults remains unresolved. The conflicting associations between adiposity and sarcopenia, ranging from apparently protective to harmful effects, have been described as the "obesity paradox". We investigated whether this paradox could be explained by heterogeneity in muscle functional capacity, hypothesising that the adiposity-sarcopenia relationship is modified by relative grip strength (RGS). Methods We conducted a cross-sectional analysis of the China Health and Retirement Longitudinal Study (CHARLS; n=15,701), with independent external validation in the US National Health and Nutrition Examination Survey (NHANES; n=10,730). RGS was defined as maximal grip strength divided by body weight. To minimise selective reporting, we performed a prespecified systematic screen of 536 interaction terms derived from 10 anthropometric exposures, 33 functional modifiers, and two sarcopenia outcomes. Core findings were evaluated through cross-metric and cross-outcome replication, sensitivity analyses addressing concerns regarding diagnostic circularity and mathematical coupling, and mediation analyses exploring potential biological pathways. Findings Among 536 tested interactions, 36 met the Bonferroni-corrected significance threshold, and 32 (89%) involved grip-related modifiers. The interaction between waist circumference and RGS for possible sarcopenia was highly significant (p=6.19 x 10(-24)). Stratified analyses showed that higher adiposity was associated with lower odds of sarcopenia, but the magnitude of this association differed substantially by RGS. For BMI, the inverse association was approximately 10-fold stronger among individuals with high RGS than among those with low RGS (OR 0.64, 95% CI 0.60-0.69 vs OR 0.97, 95% CI 0.96-0.98). Similar effect modification patterns were observed across four anthropometric measures and both sarcopenia outcomes, and were independently replicated in NHANES (p<1.0 x 10(-16)). The interaction was no longer evident after restricting analyses to participants with preserved grip strength (p=0.65). Mediation analyses suggested that the association was predominantly direct, with triglycerides accounting for 10.5% of the total effect. Interpretation The association between adiposity and sarcopenia is strongly modified by relative grip strength and appears to be concentrated among individuals with preserved muscle functional capacity. These findings provide a potential explanation for heterogeneity underlying the obesity paradox and suggest that integrating grip strength assessment into adiposity evaluation may improve risk stratification for sarcopenia in older adults.

Postoperative resilience varies widely among older adults, yet the biological drivers of recovery remain unclear. We evaluated whether preoperative immune profiles, measured in plasma and through ex vivo whole blood stimulation, predict resilience to the acute stress of total knee arthroplasty. A total of 152 adults (greater or equal to 60 years) in the PRIME KNEE cohort underwent elective total knee arthroplasty and had available blood samples for measurement of 45 immune biomarkers, quantified in plasma and in whole blood stimulated ex vivo for 24 hours with lipopolysaccharide (LPS) or influenza antigen (FLU). Resilience was assessed using Expected Recovery Differential (ERD) and Resilience Trajectory (RT) across pain severity, pain interference, lower extremity physical activities of daily living (LE PADLs), and step counts. An exploratory stability selection framework using LASSO identified biomarker predictors of postoperative outcomes. Plasma and stimulated biomarkers showed broadly similar predictive performance. A shared set of biomarkers, including LBP, leptin, TNFR1, CD30, and LIF, was consistently selected across models. Immune predictors explained ~12-24% of the variance in resilience outcomes. Distinct immune signatures emerged for pain versus functional recovery: pain related predictors mapped to local inflammatory and neuroimmune pathways, whereas function related predictors reflected systemic inflammatory load and cytokine signaling. Preoperative immune biomarkers, whether measured in plasma or after ex vivo stimulation, capture meaningful variance in postoperative resilience. The divergence between pain related and function related immune signatures highlights biologically distinct pathways underlying different dimensions of recovery and supports further development of immune based perioperative risk assessment.

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of heart failure. With improved survival from disease-modifying therapies, an increasing number of patients are presenting for surgery and may be at increased risk of adverse postoperative outcomes. This study reports outcomes of ATTR-CM patients undergoing surgery and evaluates the utility of the Revised Cardiac Risk Index (RCRI), a perioperative risk tool. Methods: A total of 145 ATTR-CM patients were included, among which 51 patients underwent at least one eligible surgical procedure. Preoperative risk was assessed using the RCRI, analyzed both as a categorical and as a dichotomized ({greater than or equal to}3 vs <3) variable. Postoperative outcomes included unplanned hospital admission, length of stay (LOS), prolonged hospitalization (>48 hours), and major adverse cardiac events. Models were adjusted for frailty (Clinical Frailty Scale {greater than or equal to}5) and major surgery, using multivariable, ordinal, and Firth penalized logistic regression analyses. Results: Patients were predominantly male (86%) with a mean age of 76 {plus minus} 9 years, and 61% were frail. Higher RCRI scores were associated with unplanned postoperative hospital admission (RCRI {greater than or equal to}3: adjusted OR 48.9, 95% CI 4.8-502.2) and longer LOS (RCRI {greater than or equal to}3: adjusted OR 40.7, 95% CI 4.3-382.8). RCRI {greater than or equal to}3 was also associated with prolonged hospitalization (>48 hours) in Firth penalized logistic regression, whereas frailty was not independently associated. Conclusions: In a real-world ATTR-CM cohort undergoing major non-cardiac surgery, the overall risk of adverse outcomes was low, and higher RCRI scores were associated with increased postoperative hospital admission and longer LOS, including hospitalization exceeding 48 hours. The RCRI retains prognostic utility in this high-risk cohort and may support peri-operative risk stratification.

Background: Heart failure (HF) is a prevalent and often debilitating cardiovascular condition among older adults, frequently accompanied by multimorbidity, functional limitations, and the need to age in place. Traditional models of successful aging emphasize disease absence and preserved function, yet most individuals with HF live with ongoing symptoms and chronic health challenges. How older adults with HF define aging well, particularly across different socioeconomic contexts, remains underexplored. Objectives: To explore how older adults with HF conceptualize aging well and to identify perceived facilitators and barriers across more and less resourced New York City neighborhoods. Methods: We conducted semi-structured interviews with 20 adults diagnosed with HF residing in Manhattan and Brooklyn neighborhoods classified by 2019 United States Census data. Interviews were guided by Rowe and Kahn's model. Transcripts were analyzed using an inductive-deductive thematic approach and interpreted in alignment with the Healthy People 2030 framework. Results: Participants had a mean age of 69 years; 50% identified as Black and 50% were women. Despite functional limitations, 65% reported aging well. Five themes emerged: maintaining physical function, maintaining cognitive function, sustaining social relationships, avoiding pain, and promoting overall well-being. Avoiding pain and promoting well-being extended beyond traditional models. Neighborhood context shaped priorities, with financial stability emphasized in more affluent areas and social cohesion prioritized in less affluent communities. Conclusions: Older adults with HF frequently perceive themselves as aging well despite chronic illness, reframing successful aging beyond disease avoidance. These findings support a patient-centered, place-informed model of aging well with implications for healthcare delivery and policy.

Background: Preoperative risk assessment in vascular surgery relies on clinical scores and lipids that do not capture atherosclerotic disease activity. Circulating fatty acid synthase (cFAS) is a liver-derived enzyme whose concentration correlates with arterial plaque FAS content independent of LDL. The 5-item modified frailty index (mFI-5) is a validated predictor of postoperative mortality. Whether cFAS predicts outcomes after vascular surgery, and whether combining it with the mFI-5 improves risk discrimination, have not been examined. Methods: We studied 657 patients undergoing elective vascular surgery at a single center (2014 to 2023). cFAS was classified as non-detectable (n = 306) or, among detectable values, by tertiles (n = 117 each). Multivariable Cox models assessed associations with major adverse events (MAE), major adverse cardiovascular events (MACE), major adverse limb events (MALE), reintervention, and mortality, and Harrell's C-statistic quantified the incremental discrimination gained by adding cFAS and the mFI-5 to standard clinical covariates. Results: High serum cFAS was independently associated with 5-year MAE (adjusted hazard ratio [aHR] 1.94; 95% CI 1.31- 2.85), mortality (aHR 1.77; 1.05 to 3.00), MALE (aHR 4.53; 2.04 to 10.05), and reintervention (aHR 2.50; 1.37 to 4.57), but not MACE. Severe frailty (mFI-5 of 3 or higher) was associated with MACE (aHR 2.69; 1.29 to 5.58) and MAE (aHR 2.46; 1.30 to 4.65) but not limb endpoints at 1 year. Adding cFAS raised the 1-year MALE C-statistic from 0.649 to 0.764; the combined model yielded the highest discrimination. Conclusions: cFAS and mFI-5 were independently and additively associated with adverse outcomes after elective vascular surgery. cFAS was associated with limb events and mortality, the mFI-5 with cardiovascular events. Combining them improved discrimination over standard covariates.

Frailty is a common consequence of aging that makes individuals increasingly susceptible to adverse health outcomes. Frailty screening can identify pre-frail and frail individuals to prescribe interventions or inform clinical decision making to prevent or slow additional frailty progression. Objective, scalable, and automated frailty assessments may expedite and improve clinical frailty screening. Here, we leveraged human pose estimation for video-based gait analysis in older adults who were non-frail, pre-frail, and frail. We focused on gait because slow walking speed is key diagnostic criteria of frailty, and many gait deviations are often observed in older adults with frailty. We collected videos of 68 older adults (25 non-frail, 25 pre-frail, 18 frail) walking at both self-selected and fast paces and used an established pose estimation-based gait analysis approach to measure and compare gait parameters across frailty statuses. Pose estimation-based step time measurements were strongly correlated with manual annotations (self-selected: R2=0.93, fast: R2=0.80) and showed tight Bland-Altman limits of agreement (self-selected: -0.082 to 0.052s, fast: -0.114 to 0.110s), establishing validity of this video-based gait analysis approach in older adults. We then identified a series of cross-sectional differences in spatiotemporal gait parameters among non-frail, pre-frail, and frail older adults, demonstrating that video-based gait analysis can be useful for measuring gait differences across frailty statuses. This study demonstrates the potential of video-based pose estimation for scalable gait tracking across frailty statuses in older adults.

Background: It is unclear if sex differences exist in cognitive impairment and dementia associated with atrial fibrillation (AF) and whether this relationship is influenced by oral anticoagulation (OAC) therapy. Methods: We identified patients [&ge;]40 years with incident non-valvular AF (NVAF) and without previous history of cognitive impairment or dementia, stroke/transient ischemic attack or contraindication to OAC between April 1st, 2012 and March 31st, 2024, using linked administrative databases in Alberta, Canada. Outcomes included cognitive impairment, Alzheimer's disease, vascular dementia, and all-cause mortality. Survival models were used to estimate association between sex and outcomes, and between OAC therapy and outcome stratified by sex. Results: Of 66,885 patients, 43% were female. Compared to males, females were older (74 vs 68 years), frailer (14.7% vs 10.1%), and more likely to have CHA2DS -VA score [&ge;]2 (73% vs 65%). OAC was initiated in 60% of both sexes within 120 days of diagnosis. Females had a higher risk for cognitive impairment (aHR 1.14 [95% CI 1.07-1.20], p<0.0001), but a lower risk of vascular dementia (aHR 0.75 [95% CI 0.63-0.90], p=0.0016) and all-cause mortality (aHR 0.91 [95% CI 0.88-0.94], p<0.001), with no difference in risk of Alzheimer's disease (aHR 1.01 [95% CI 0.88-1.17], p=0.8496) between the sexes. Non-vitamin-K OAC (NOAC) use was associated with a lower risk of cognitive impairment compared to either warfarin or no OAC in both sexes, but a lower risk of Alzheimer's and vascular dementia in males only. Conclusion: In this large population-based study, we found females have a higher risk of cognitive impairment, but a lower risk of vascular dementia and all-cause mortality compared to males. For both sexes, NOAC use was associated with a lower risk of cognitive impairment compared to no OAC and a lower risk of Alzheimer's and vascular dementia in males only.

Introduction Frailty is an ageing-related state associated with disability and mortality. Women often experience higher frailty but lower mortality than men, a pattern described as the male-female health-survival paradox. Evidence from low- and middle-income settings is limited. We examined sex differences in frailty trajectories and terminal decline in Mexico. Methods We analysed five waves (2001-2018) of the nationally representative Mexican Health and Aging Study (MHAS) including 12,440 adults ([&ge;]50 years at baseline). Frailty was measured using a 31-deficit frailty index (FI score; 0-1). We used survey-weighted linear mixed-effects models with time interactions, adjusted for sociodemographic, behavioural and health covariates to model sex differences in frailty trajectories. Terminal decline in FI was modelled among those who died using mixed-effects models on the time-to-death scale. Results A total of 12,440 adults aged 50 to 105 years were included, with a mean age of 62.1 years (SD 9.6); 5,698 men (45.8%) and 6,742 women (54.2%). Mean baseline FI was 0.17 (SD 0.12), higher in women than men (0.19 vs 0.16; P<0.001). After adjusting, women had a 0.014 higher mean FI than men at baseline (adjusted mean difference; 95%CI 0.008, 0.020), with difference widening over follow-up, increasing from 0.016 at 2 years to 0.029 at 17 years. Analysis of terminal decline found that accumulation of frailty accelerated in the years preceding death; with results suggesting that women reached death with higher frailty than men (difference 0.029; 95%CI 0.009, 0.048). Conclusion Women experienced higher and more rapidly increasing frailty compared to men and carried a greater frailty burden in the years preceding death. These findings underscore the importance of considering sex differences in frailty trajectories when developing healthy ageing strategies that address the life-course vulnerabilities disproportionately driving frailty accumulation in women in low- and middle-income countries.

Background: Peripheral artery disease (PAD) is an occlusive arterial disease primarily affecting the lower extremities. It impacts over 230 million people worldwide and is associated with significant morbidity and mortality. The ankle brachial index (ABI) test is a non-invasive method to detect PAD that compares the blood pressure in the ankle and arm to evaluate lower extremity blood flow. An estimated 20-50% of individuals with detectable PAD are asymptomatic and remain undiagnosed; however, ABI screening in high-risk, asymptomatic populations is not currently guideline-recommended. Few studies have evaluated change in ABI over time in asymptomatic populations. Therefore, we aimed to identify distinct trajectories of ABI values from mid- to late-life. Methods: We utilized data from the Atherosclerosis Risk in Communities (ARIC) study; a longitudinal cohort study initiated in 1987 that enrolled 15,792 participants aged 45-64. ABI measurements were collected at five visits over a 30-year period. We used group-based trajectory modeling to identify trajectories of ABI from mid- to late-life. Final model selection was based on visual fit, statistical criteria, group sizes, and substantive knowledge. Lastly, we compared baseline demographics, social determinants of health, and overall cardiovascular (CV) health, assessed using the American Heart Association's Life's Essential 8 (LE8) framework, across trajectory groups. Results: We identified 4,121 participants with ?3 ABI measurements over the study period in at least one limb. At baseline, participants had an average age of 51.4 {+/-} 4.9 years, were 57.3% female, 22.2% Black, and had an average overall LE8 score of 68.0 {+/-} 13.9 points. Our final model identified three linear trajectories: low-normal, high-normal, and declining. Overall LE8 scores varied significantly across trajectory groups: 67.3 {+/-} 10.7 (high-normal), 61.9 {+/-} 13.3 (low-normal), and 50.1 {+/-} 15.8 points (declining). Women had lower average ABI values, were more likely to experience a declining ABI trajectory, and had a delayed onset of decline compared to men. A greater proportion of Black participants experienced declining ABIs, with earlier, faster, and more severe declines than White participants. Conclusions: Poor overall CV health and common CV risk factors are associated with ABI decline. Targeted ABI screening in middle age may help detect PAD in its beginning stages and support early intervention.

Background Evidence on frailty progression following severe infections is limited. We compared rates of transition to greater frailty or death between adults with and without severe infection in England. Methods We conducted a matched-cohort study among adults aged [&ge;]65 years (1,452,117: median age 76 years, 45% male) in Clinical Practice Research Datalink Aurum (2006-2019). Adults with severe infection (hospitalised primarily due to infection) were matched on calendar time to individuals without severe infection on age, sex, and primary care practice. The admission date was used as index date and same was assigned to matched unexposed adults. We measured frailty using Electronic Frailty Index, a proportion of 36 health deficits in validated categories (Fit 0-0.12, Mild >0.12-0.24, Moderate >0.24-0.36, Severe >0.36). In a time-varying Markov multistate model, we focused on forward transitions from baseline or intermediate frailty states to higher states or death. For each transition, we used Cox regression to estimate cause-specific transition hazard ratios (HR) with 95% confidence intervals (CIs), comparing adults with and without severe infection. We adjusted for baseline frailty score, age, sex, deprivation, harmful alcohol use, smoking, and primary care infection history 5 years before index date. We estimated state occupancy probabilities, and expected length of stay (ELOS) in each state at year five among adults with and without severe infection. We explored effect modification by infection type. Results Across all transitions, severe infection was associated with higher adjusted hazards of transitioning to worsening frailty or death, HR, 95% CI: (fit to: mild[1.56, 1.54-1.58], moderate[2.51, 1.79-3.51], death[4.57, 4.50-4.65]; mild to: moderate[1.52, 1.50-1.53], severe[1.90, 1.43-2.52], death[2.67, 2.64-2.70]; moderate to: severe[1.40, 1.38-1.42], death[1.87, 1.85-1.90]; severe to death[1.48, 1.46-1.50]). Transition hazard ratios were strongest for lower respiratory tract infections, followed by sepsis, urinary tract infections, meningitis/encephalitis, gastroenteritis, and skin and soft tissue infections. At five years, adults with severe infection had higher probabilities of transitioning to greater frailty or death across all transitions and lower ELOS in each frailty state than those without severe infection. Interpretation Severe infections may accelerate frailty deterioration in older age. Prevention through vaccination, early detection, and prompt management may help mitigate this decline.