The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"Immune status modifies the association between plasma zonulin-1 and skeletal-related events in treated HIV: a case-cohort study.","authors":"Carlos Pita-Martínez, Marta Rava, Ana Muñoz-Gomez, Melchor Riera, Joaquim Peraire, María Novella-Mena, Sergio Guillén Martínez, Marta Montero-Alonso, María Ángeles Jiménez-Sousa, Salvador Resino, Rubén Martín-Escolano, CoRIS Cohort","doi":"10.1093/gerona/glag186","DOIUrl":"10.1093/gerona/glag186","url":null,"abstract":"<p><p>Chronic inflammation driven by microbial translocation is implicated in the increased risk of skeletal-related events (SREs) among people with HIV (PWH) on antiretroviral therapy (ART). We aimed to assess the association between plasma biomarkers of gut barrier dysfunction and incident SREs in PWH on suppressive ART, and whether the host's baseline immune status modifies this association. We employed a nested case-cohort design within the Spanish CoRIS cohort. We quantified baseline plasma markers (zonulin-1, LPS, LBP, and flagellin) in 65 incident SRE cases and a randomly selected subcohort of 263 PWH. Borgan II-weighted Cox regression models were used to test for associations and interactions between log2-transformed biomarkers and baseline CD4+ T-cell counts (< 500 vs ≥ 500 cells/mm³). In the overall population, zonulin-1 was not significantly associated with SRE risk (aHR 1.54; 95% CI, 0.90-2.62). However, we detected a significant interaction between zonulin-1 and immune status (interaction p < .001). In participants with suboptimal immune recovery (CD4+ <500 cells/mm³), higher zonulin-1 levels were associated with incident SREs (aHR 5.14; 95% CI, 2.25-11.77; interaction q < .001). Conversely, this association was absent in participants with preserved immune status (CD4+ ≥500 cells/mm³; aHR 0.98; 95% CI, 0.58-1.67). LPS, LBP, and flagellin showed no association with SREs regardless of immune status. Gut barrier dysfunction, measured by plasma zonulin-1, is associated with a higher risk of SREs; however, this association is restricted to PWH with incomplete immune reconstitution. These findings support a \"two-hit\" model in which immune competence and aging modulate the skeletal consequences of gut leakage.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frailty, polypharmacy, deprescribing, and 23-hour activity: insights from a mouse model.","authors":"John Mach, Kevin Winardi, Sarah N Hilmer","doi":"10.1093/gerona/glag170","DOIUrl":"10.1093/gerona/glag170","url":null,"abstract":"<p><p>Management of older people with frailty commonly includes polypharmacy and deprescribing. The impacts of frailty on the outcomes of medication use and deprescribing are poorly understood, as are the effects of medication use and deprescribing on frailty and function. Here, using aged C57BL/6J (B6) male mice, we explore the effects of different chronic drug regimens (polypharmacy and monotherapy) and deprescribing on daily activities using an automated behavioral recognition cage and explore the relationship with frailty and trajectories. At 12 months, male C57BL/6 mice were chronically administered a control diet, 1 of 5 monotherapy diets, or 1 of 3 polypharmacy diets with an increasing Drug Burden Index (measure of total exposure to sedative and anticholinergic medications). At 21 months of age, mice were stratified to continue treatment or to have treatment gradually withdrawn (deprescribed). At 24 months, mice were assessed using the Laboratory Animal Behavior Observation Registration and Analysis System (LABORAS) automated animal behavioral recognition system for 23 hours. We found that polypharmacy with increasing DBI substantially altered activity and could not be extrapolated from monotherapy response. After deprescribing, while some of the drug effects were reversible, others were irreversible, and we observed some novel changes. Exploring the relationship between frailty and LABORAS behavioral outcomes revealed unique correlations for each intervention group. Four key clusters were identified with different frailty trajectories and attributes, deficits, and LABORAS outcomes. This preclinical study demonstrates that medication use and deprescribing can impact activity, frailty, and frailty trajectories. The context of polypharmacy and deprescribing are important considerations to enhance translation of preclinical studies of frailty.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical activity and sitting over 9 years of the Women's Health Initiative Strong & Healthy (WHISH) randomized physical activity intervention trial in older women.","authors":"Marcia L Stefanick, Sally F Mackey, Joseph C Larson, Lesley F Tinker, Valerie McGuire, Corey M Rovzar, Marily Oppezzo, Michael J LaMonte, Charles Kooperberg, Andrea Z LaCroix, Abby C King","doi":"10.1093/gerona/glag189","DOIUrl":"10.1093/gerona/glag189","url":null,"abstract":"<p><strong>Background: </strong>The Women's Health Initiative (WHI) Strong & Healthy (WHISH) randomized trial implemented a 9-year remotely delivered \"light touch\" multicomponent physical activity intervention (PA-I) aimed at increasing physical activity (PA) and reducing sitting time in a large U.S. cohort of older women.</p><p><strong>Methods: </strong>Using a randomized consent design, 49 331 women, aged 66-99 years, were assigned to Intervention (N = 24 657), 95.9% (N = 23 653) of whom provided passive consent to receive the WHISH PA-I, or \"usual activity\" Comparison (N = 24 674). Differences between intention-to-treat arms in self-reported walking, sitting and other PA, averaged over the course of the trial, were derived from a linear regression model with log-transformed outcomes as a function of arm, adjusted for participant selection strata.</p><p><strong>Results: </strong>Pre-randomization mean age (79.7 years), total recreational PA (11.6 MET-hours/week), RAND-36 physical function score, and other characteristics did not differ between trial arms. Over a median 8.7 years, Intervention participants reported higher average walking (3.2%), aerobic (3.4%), and total (3.7%) exercise, as MET-hours/week, and strength training sessions per week (4.4%), and fewer hours/week of sitting (1.5%) than Comparison (p < .001 for all). Intervention versus Comparison differences were greater for aerobic exercise (6.92%) and sitting (-2.48%) in the youngest age group (66 - 76) compared with other age groups (p <.001 and .02 for interaction , respectively).</p><p><strong>Conclusion: </strong>A 9-year \"light touch\" remotely-delivered PA intervention modestly attenuated age-related PA decreases and sitting time increases in older women. Building on the pragmatic WHISH PA intervention to augment behavioral changes, especially in adults aged over 80 years, is an important direction for population health.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Late-life disability following the action for health in diabetes (Look AHEAD) trial.","authors":"","doi":"10.1093/gerona/glag195","DOIUrl":"https://doi.org/10.1093/gerona/glag195","url":null,"abstract":"","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":"81 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leisure-time physical activity and metabolomic trajectories over the transition from late midlife to old age.","authors":"Katri Ruutu, Jens Verbeeren, Tuija M Mikkola, Merja K Laine, Johan G Eriksson, Niko S Wasenius","doi":"10.1093/gerona/glag159","DOIUrl":"10.1093/gerona/glag159","url":null,"abstract":"<p><p>Physical activity may counteract aging-associated disruptions in the metabolome. We investigated how leisure-time physical activity (LTPA) associates with the metabolome in late midlife and with 15-year metabolomic trajectories. The study included 1816 Helsinki Birth Cohort Study participants at baseline (mean age 61.6 years), with 985, 996, and 740 participants at the 5-, 10-, and 15-year follow-ups, respectively. LTPA was assessed at baseline and after 15 years using a validated questionnaire and expressed as METhours/week. Nuclear magnetic resonance-based metabolomics data from fasting blood samples were used to analyze 161 biomarkers at baseline and at each follow-up. Weighted Gene Co-Expression Network Analysis was performed on the metabolomics data to identify 11 metabolomic biomarker modules. Baseline associations were analyzed using restricted cubic splines and longitudinal associations with linear mixed-effects models. Analyses were sex-stratified, covariate-adjusted, and corrected for multiple testing. At baseline, LTPA was nonlinearly associated with albumin in women and with 9 biomarkers in men in the crude, but not fully adjusted, model. Over the follow-up, baseline LTPA was associated with the age-related trajectory of triglyceride-enriched high-density lipoprotein (HDL) module in men (age × LTPA interaction p = .041). In the high LTPA group, the trajectory declined significantly compared to the low (p = .004) and moderate LTPA groups (p = .045). No associations were found in women. To conclude, in men, higher LTPA in late midlife predicted a favorable 15-year trajectory of triglyceride-enriched HDL. Our findings indicate that an active lifestyle is associated with more favorable metabolomic trajectories related to cardiometabolic health across late midlife and old age.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A technology-blended exercise intervention for cognitive risk reduction and brain health in middle-aged and older adults with type 2 diabetes in Singapore: a mixed-methods study.","authors":"Jinghua Zhang, Wilson Wai San Tam, Jinhua Lu, Junjie Chen, Jed Montayre, Joji Kusuyama, Yanhong Dong, Xin Yi Yap, Wentao Zhou, Na Wang, Hui Nan Yeo, Frena Jia Sy Lee, Vivien Xi Wu","doi":"10.1093/gerona/glag192","DOIUrl":"10.1093/gerona/glag192","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is a major modifiable risk factor for accelerated brain ageing, cognitive decline, and dementia. However, sustainable lifestyle interventions targeting cognitive health in at-risk older adult populations remain limited. This mixed-methods study evaluated the effects of a 12-week technology-blended Intensive Aerobic and Resistance Exercise Program (IAREP) on cognitive risk and related health outcomes among middle-aged and older adults with T2DM in a primary care setting in Singapore.</p><p><strong>Methods: </strong>Participants were recruited from a community polyclinic and allocated to either the intervention or usual care group. The intervention integrated face-to-face, Zoom-based, and video-recorded home exercise sessions to support accessibility and adherence. Quantitative outcomes included cognitive impairment (CI) risk, physical function, metabolic and inflammatory markers, physical activity, and self-care maintenance. Qualitative focus group discussions (FGDs) explored participant experiences following program completion.</p><p><strong>Results: </strong>Fifty-three participants completed the study (mean age 66.7 years). Compared with usual care, the intervention group demonstrated significant reductions in predicted risk of CI (F(1,51) = 4.9, p = .031, η²p = 0.088), improvements in physical function (F(1,51) = 10.6, p = .002, η²p = 0.172), and higher physical activity levels (F(1,51) = 8.3, p = .006, η²p = 0.140). Self-care maintenance also improved significantly (F(1,51) = 4.5, p = .040, η²p = 0.081). Adherence was high (88.9%). Qualitative findings highlighted enhanced motivation, social connectedness, and perceived cognitive and physical well-being.</p><p><strong>Conclusions: </strong>These findings support technology-blended exercise might be a feasible and scalable strategy for cognitive risk reduction and brain health promotion among middle-aged and older adults with T2DM, with potential translational relevance for dementia prevention in primary care and community settings.</p><p><strong>Clinical trial registration number: </strong>NCT06401733.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-year disability trajectories and associated factors among adults aging with HIV in the Ontario HIV Treatment Network Cohort Study.","authors":"Tai-Te Su, Lisa Avery, Ahmed M Bayoumi, Soo Chan Carusone, Ada Tang, Tsegaye Bekele, Francisco Ibáñez-Carrasco, George M Da Silva, Puja Ahluwalia, Adrian Betts, Kiera McDuff, Ivan Ilić, Annamaria Furlan, Kelly K O'Brien","doi":"10.1093/gerona/glag185","DOIUrl":"10.1093/gerona/glag185","url":null,"abstract":"<p><p>Disability among adults aging with HIV may be episodic and change over time. Guided by the Episodic Disability Framework, we examined disability trajectories, year-to-year fluctuations, and contextual factors associated with disability among adults aging with HIV over time. Annual disability data were collected from participants in the Ontario HIV Treatment Network Cohort Study (OCS) between 2019 and 2023 (n = 1896; 6524 person-years). Disability severity was measured using the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0). Growth mixture modeling identified distinct disability trajectories, and year-to-year fluctuations were quantified using the intraindividual interquartile range (iIQR). We applied multinomial logistic regression to examine factors associated with disability trajectories. The mean age of participants was 51.8 ± 12.1 years, 77% were men, and 58% were White. The mean duration since HIV diagnosis was 16.5 ± 9.3 years. Three disability trajectories were identified: low disability (28.2%), moderate disability (53.0%), and high disability (18.9%). Disability fluctuations increased across trajectories, with the smallest variability observed in the low disability trajectory (average iIQR = 0.22) and greater variability in the moderate (2.82) and high (4.55) disability trajectories. Factors associated with the high disability trajectory included identifying as a woman, lower income, smoking, recent substance use, no alcohol use, greater comorbidity, and higher HIV stigma. Older age, identifying as Black, higher income, and greater social support were associated with the low disability trajectory. Adults aging with HIV experienced heterogenous and dynamic disability trajectories. Modifiable factors including health behaviors, stigma, and social support may influence disability over time.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compositional data analysis of 24hr activity and its associations with muscle strength and power: The Study of Muscle, Mobility and Aging.","authors":"Lauren S Roe, Elsa S Strotmeyer, Peggy M Cawthon, Nancy W Glynn, Reagan E Garcia, Yan Ma, Megan Hetherington-Rauth, Nina Z Heilmann, Kelley P Gabriel, Stephen B Kritchevsky, Jane A Cauley","doi":"10.1093/gerona/glag188","DOIUrl":"10.1093/gerona/glag188","url":null,"abstract":"<p><strong>Background: </strong>Physical activity (PA) and inactivity have opposing associations with skeletal muscle function and are often studied separately but are codependent. We evaluated cross-sectional associations between 24-h time-use behaviors with muscle strength and power.</p><p><strong>Methods: </strong>Sample included 751 community-dwelling older adults (76 ± 5 years, 57% women). Compositional data analysis determined 24-h proportions of time in moderate-to-vigorous PA (MVPA) and light intensity PA (LPA), inactivity, and sleep. Multiple linear regression by sex evaluated associations between 24-h composition with stair climb ascend and leg press power (W), and leg press (lbs) and grip strength (kg). Compositional isotemporal substitution quantified hypothetical reallocations of time between behaviors on power and strength.</p><p><strong>Results: </strong>Compared to the average 24hr day in women (MVPA: 84 min/day, LPA: 349 min/day, inactivity: 559 min/day, sleep: 448 min/day), higher 24-h proportions of MVPA were associated with higher stair climb power (β: 16.2, 95% CI: 10.9, 21.4), leg press power (β: 23.7, 95% CI: 10.3, 37.2), and leg strength (β: 8.5, 95% CI: 2.4, 14.6); higher 24-h proportions of LPA were associated with lower stair climb power (β: -14.4, 95% CI: -25.8, -3.0); and higher 24-h proportions of inactivity were associated with higher grip strength (β: 2.3, 95% CI: 0.4, 4.3). Compositional isotemporal substitution found reallocating 10 min from LPA or inactivity to MVPA supported higher power and strength. No associations were observed in men.</p><p><strong>Conclusions: </strong>In women, not men, 24-h movement composition was associated with power and strength. MVPA interventions for power and strength improvements in women may be optimized when LPA or inactivity are reduced, not sleep.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Satellite-based evidence for heatwave-driven MCI-to-dementia transitions.","authors":"Sun-Bi Um","doi":"10.1093/gerona/glag190","DOIUrl":"10.1093/gerona/glag190","url":null,"abstract":"<p><p>This study aimed to provide satellite-based evidence on the potential role of heatwave exposure in the transition from mild cognitive impairment (MCI) to dementia by examining whether heatwave exposure statistically modifies the association between MCI and dementia prevalence using repeated district-level observations collected annually from 228 administrative districts across South Korea between 2015 and 2023. Satellite-derived land surface temperature from the Moderate Resolution Imaging Spectroradiometer (MODIS) thermal imagery was used as a proxy for heatwave exposure. Interaction-based modeling was implemented by multiplying MCI prevalence by summer temperature to construct interaction terms. Heatwave exposure, MCI prevalence, and their interaction term were specified as independent variables in a geographically and temporally weighted regression (GTWR) model, with dementia prevalence serving as the dependent variable. The results revealed spatial variation in how heatwave exposure moderates the MCI-dementia progression, particularly in districts where the proportion of older adults exceeded 25%, suggesting an accelerated transition to dementia in these areas. Although this study focused on South Korea, the findings may offer relevant insights for other countries into how heatwave exposure interacts with regional patterns of dementia risk.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating frailty index integrity: insights from an international network study.","authors":"Robert Cavanaugh, Chelsea Wong, Louisa H Smith, Maytal Bivas-Benita, Pinchas Akiva, Tal El-Hay, Ariela R Orkaby, Chen Yanover, Brianne Olivieri-Mui","doi":"10.1093/gerona/glag193","DOIUrl":"10.1093/gerona/glag193","url":null,"abstract":"<p><strong>Background: </strong>Deficit-accumulation frailty indices (FIs) have rapidly been integrated into health systems worldwide to quantify the state of reduced physiologic reserve to recover from a health insult in the aging population. Common data models (CDMs) have further enabled international, interinstitutional applications of FIs. However, the validity of such applications is unknown. The objective of this study was to evaluate the validity of 2 common FIs across disparate contexts.</p><p><strong>Methods: </strong>We conducted an international network study comparing estimates of frailty prevalence from 2 electronic health record (EHR)-based FIs: United States-based Veterans Affairs FI (VAFI) and United Kingdom-based electronic FI (eFI) across 5 research and clinical databases. United States: All of Us (n = 159 721), IQVIA Pharmetrics+ (n = 5 099 557); United Kingdom: IMRD-THIN (n = 3 036 003), IMRD-EMIS (n = 832 455), and BioBank (n = 207 202).</p><p><strong>Results: </strong>In US databases, VAFI identified higher proportions of frailty ([VAFI; eFI] All of US: 10.3%; 2.5%, Pharmetrics+: 9.6%; 2%) while in UK databases, the eFI identified higher proportions (IMRD-THIN: <0.003%; 0.08%, IQVIA-EMIS: 0.09%; 0.4%, UK BioBank: 0.03%; 0.1%). Additional manipulations (alternative lookback periods, FI variations) were examined.</p><p><strong>Conclusions: </strong>Frailty prevalence across databases and indices was inconsistent with expected frailty measurement trends. FIs are likely dependent on their development context, such as local coding behaviors and incentives, limiting their external validity despite CDM harmonization. We suggest caution in the application of FIs outside of their development context and recommend further instrument development before more widespread application of FIs using CDMs.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}