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

{"title":"Longitudinal Association Between Prefrailty/Frailty and HIV-associated Neurocognitive Disorder (HAND): a Mexican Prospective Study.","authors":"Jorge Arturo Esteva López, Neftali Eduardo Antonio-Villa, Marielena Esponda Farfan, José Alberto Avila-Funes, Virgilio Hernandez-Ruiz","doi":"10.1093/gerona/glag251","DOIUrl":"https://doi.org/10.1093/gerona/glag251","url":null,"abstract":"<p><p>Geriatric syndromes such as frailty may be more prevalent and occur earlier in people aging with HIV, negatively impacting outcomes like cognition. Cross-sectional data show strong associations between pre-frailty/frailty and HIV-associated neurocognitive disorders (HAND). However, prospective studies suggest baseline HAND increases frailty risk, while pre-frailty/frailty do not predict HAND onset. We aimed to investigate longitudinal association between baseline frailty and HAND category progression. Longitudinal analysis of 194 participants aged ≥50 years from Mexico City referral center. Two standardized geriatric assessments performed at least one year apart. HAND defined using Antinori criteria, frailty by Fried phenotype. Inverse probability weighted Cox models adjusted for confounders from directed acyclic graph (age, educational level, detectable viral load, diabetes, stroke, ischemic heart disease) determined association between frailty and HAND progression. Median age 55 (53-61) years; 167 (86%) men; median follow-up 2.3 (1.6-3.1) years. Baseline: 129 (66.4%) robust, 62 (31.9%) pre-frail, 3 (1.5%) frail. No longitudinal association between pre-frailty/frailty and HAND progression was observed in this cohort (32 progression events; adjusted HR = 0.63, 95% CI 0.27-1.48; p = 0.29). No evidence of a prospective association between prefrailty/frailty and HAND category progression was observed in this cohort; most participants remained cognitively stable. To our knowledge, this is the first study describing HAND trajectories and their relationship with prefrailty/frailty in older adults with HIV in Mexico and Latin America.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229656","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":"Intrinsic Capacity in a Nationally Representative US Population.","authors":"Stephanie Denise M Sison, Lan Luo, Sunyoung Kim, Kevin Pritchard, Dae Hyun Kim, Sandra Shi","doi":"10.1093/gerona/glag247","DOIUrl":"https://doi.org/10.1093/gerona/glag247","url":null,"abstract":"<p><strong>Background: </strong>Intrinsic capacity (IC) is defined by the World Health Organization as the sum of an individual's physical and mental abilities that support health and well-being. While well validated internationally, it has not been operationalized and validated in a nationally representative US cohort.</p><p><strong>Methods: </strong>Using data from 5,834 community-dwelling older adults from Round 12 (2022) of the National Health and Aging Trends Study (NHATS) survey, we identified measures related to IC domains (cognition, locomotion, vitality, psychological, sensory). We performed exploratory factor analysis (EFA), omega hierarchical reliability testing, and confirmatory factor analysis (CFA) using bi-factor and second-order structures. We also constructed the Integrated Care for Older People (ICOPE) screening tool. Descriptive statistics and regression models were used to examine the associations of IC and ICOPE scores with demographic and health characteristics. Age- and sex-specific reference centile curves were developed using empirical percentiles.</p><p><strong>Results: </strong>EFA consistently supported a six-factor structure (vision and hearing were separate). Omega hierarchical analysis supported a strong general factor (ω = 0.92; ωₕ=0.72), and the bi-factor model demonstrated excellent fit. IC and ICOPE scores showed strong correlation (r = 0.71). Higher IC scores were associated with younger age, higher level of education, and income. Prevalence of comorbidities, frailty, ADL and IADL disability increased from the highest to the lowest IC and ICOPE quartiles. Reference centile curves demonstrated progressive age-related decline, with females showing lower IC scores than males.</p><p><strong>Conclusion: </strong>We demonstrate IC operationalization in a nationally representative U.S. cohort and provide the first US-specific reference centile curves. The findings provide a foundation for future IC research in the US.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149372","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":"Deprescribing Fall Risk-Increasing Drugs in Older Adults: Implementation Challenges and a Conceptual Framework from the DeFRID Trial and Global Evidence.","authors":"Madhavi Eerike, Sakthivadivel Varatharajan, Priyadharsini Rajendran, Paul Mathai, Veena Nayak, Vijaya Kumar Karra, Gomathi Ramaswamy, Rekha Priyadarshini, Gerard Marshall Raj, Venugopalan Gunasekaran, Selvaraj Jayachandran, Sandhiya Selvarajan, Shivanand Kattimani, Anu Chandran, Rijesh Potangadi, Surendran Padinchara Kunhipilakkandiy, Narayanan Puthiya Veettil, Raghavendra Rao, Mukhyaprana Prabhu, Jerin Jose Cherian, Tanu Anand, Sowparnika Treasa Sabu, Lokesh Kumar Sharma","doi":"10.1093/gerona/glag248","DOIUrl":"https://doi.org/10.1093/gerona/glag248","url":null,"abstract":"<p><strong>Background: </strong>Deprescribing fall risk-increasing drugs (FRIDs) is essential for reducing polypharmacy and falls in older adults, yet randomized controlled trials (RCTs) face unique implementation challenges. The DeFRID study is an ongoing multi-center RCT evaluating an ARMOR-based deprescribing intervention versus usual care in adults aged ≥60 years prescribed FRIDs. The objectives of this review are threefold: (1) to describe practical challenges encountered during a multi-center deprescribing RCT in India; (2) to propose a conceptual framework for categorizing these barriers; and (3) to contextualize DeFRID's experience within the broader deprescribing research landscape.</p><p><strong>Methods: </strong>We conducted a narrative review with systematic scoping elements, synthesizing global RCT evidence from PubMed, OpenAlex, and Google Scholar (inception-December 2025) with DeFRID process evaluation data. DeFRID barriers and facilitators were identified via mixed-methods (clinician KAP questionnaire and qualitative interviews), team meetings, retention logs, and Phase II RCT implementation data, thematically categorized, then compared with global RCT challenges.</p><p><strong>Results: </strong>DeFRID implementation revealed four challenge categories: ethical-clinical difficulties establishing equipoise for FRID withdrawal; operational barriers to recruitment and retention; methodological complexities in fall outcome ascertainment; and context-specific constraints unique to the Indian LMIC setting-limited deprescribing guidelines, polypharmacy normalization, fragmented care coordination, and hierarchical decision-making. Global RCTs revealed substantial implementation challenges: low clinician adherence, short follow-up periods, restrictive eligibility excluding frail or cognitively impaired older adults, and resource-intensive interventions limiting scalability.</p><p><strong>Conclusions: </strong>Deprescribing FRIDs in older adults is impeded by ethical, operational, methodological, and provider-patient challenges, necessitating multilevel strategies integrating training, shared decision-making, context-specific guidelines, and stakeholder engagement for scalable implementation.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140095","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":"Performance of claims-based frailty indices in Medicare Advantage and fee-for-service populations.","authors":"Lan Luo, Kevin Pritchard, Chan Mi Park, Xiecheng Chen, Eunji G Kim, Ellen P McCarthy, Dae Hyun Kim, Sandra M Shi","doi":"10.1093/gerona/glag229","DOIUrl":"10.1093/gerona/glag229","url":null,"abstract":"<p><strong>Background: </strong>Despite growing enrollment in Medicare Advantage (MA) plans, the performance of claims-based frailty algorithms, which were developed for Medicare fee-for-service (FFS), remains unclear in MA.</p><p><strong>Methods: </strong>We calculated the Kim claims-based frailty index (CFI), Veterans Affairs-Frailty Index (VA-FI), and Hospital Frailty Risk Score (HFRS) using the National Health and Aging Trends Study linked to Medicare FFS and MA data. We evaluated their performance against the comprehensive geriatric assessment-based frailty index (CGA-FI) and the frailty phenotype (FP) in Round 11 and Round 9.</p><p><strong>Results: </strong>Among 1527 FFS and 1457 MA beneficiaries in Round 11, frailty prevalence was 34.2% and 35.5%, respectively, by CGA-FI ≥0.25, and 13.3% and 16.2%, respectively, by FP. Across FFS and MA populations, the CFI, which prioritizes specificity and positive predictive value, classified 10%-12% of the overall population and 30%-36% of those with prior hospitalization as frail, whereas the VA-FI and HFRS, which emphasize sensitivity, classified 53%-71% of the overall population and 56%-87% of those with prior hospitalization as frail. Although claims-based frailty measures performed similarly across FFS and MA populations, their discriminatory ability was higher for CGA-FI ≥0.25 (C-statistics: CFI, 0.79-0.82; VA-FI, 0.77-0.82; HFRS, 0.63-0.77) than for FP (CFI, 0.71-0.77; VA-FI, 0.67-0.75; HFRS, 0.60-0.74). Performance was consistent by race and survey rounds, with modestly better discrimination in women than men.</p><p><strong>Conclusions: </strong>Claims-based frailty measures are scalable tools for contemporary FFS and MA populations. However, applying published thresholds led to differences in frailty prevalence and model performance. Thresholds should therefore be tailored to the intended.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003314","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":"Aging-related diseases in the US population: a data-driven approach using All of Us electronic health record data.","authors":"Buwei He, Matthew Lohman, Stephanie Aghamoosa, Tiejun Zhang, Bankole Olatosi, Jiajia Zhang","doi":"10.1093/gerona/glag231","DOIUrl":"10.1093/gerona/glag231","url":null,"abstract":"<p><strong>Background: </strong>Aging is the strongest risk factor for most chronic diseases, yet aging-related diseases (ARDs) lack consistent, data-driven definitions. Prior work has proposed frameworks to classify ARDs based on age-specific onset patterns, but applications have largely relied on demographically homogeneous populations.</p><p><strong>Methods: </strong>We extended a data-driven framework integrating unsupervised clustering and actuarial modeling to electronic health record data from 633 547 participants in the US All of Us Research Program. Age-specific onset rates for 274 high-burden diseases between ages 21 and 74 were analyzed. Standardized onset curves were grouped using hierarchical agglomerative clustering. Aging-related patterns were assessed with Gompertz and Gompertz-Makeham (GM) models to quantify age-dependent increases in disease onset.</p><p><strong>Results: </strong>Eleven clusters of disease onset trajectories were identified, with 4 main clusters encompassing 96.0% of diseases. Two clusters exhibited pronounced late-life increases in onset rate, while 1 showed earlier but moderate age-related increases, and another displayed largely age-independent patterns. Cardiovascular diseases and cancers were enriched in clusters with strong aging-related onset trajectories. Overall, 165 diseases demonstrated strong evidence of being aging-related, characterized by positive Gompertz age coefficients and good GM model fit. Median onset ages varied across clusters and disease categories and showed statistically significant discrepancies compared with UK populations.</p><p><strong>Conclusions: </strong>In a large, racially diverse US cohort, we identified distinct ARD clusters with shared age-related onset patterns. These findings extend prior work to a more diverse population and support integrated clustering and actuarial approaches to systematically define ARDs and inform aging research and public health strategies.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979133","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":"Social isolation, loneliness, and cognitive decline among Black Americans: the moderating role of neighborhood context.","authors":"Ann W Nguyen, Chuwen Zhong, Kedong Ding, Cleothia Frazier, Weidi Qin, Harry Owen Taylor","doi":"10.1093/gerona/glag236","DOIUrl":"10.1093/gerona/glag236","url":null,"abstract":"<p><strong>Background: </strong>Our study examined how social disconnection, neighborhood contexts, and cognitive function trajectories are jointly and interactively associated among middle-aged and older Black adults.</p><p><strong>Methods: </strong>Data came from non-Hispanic Black participants aged 51 and older (n = 1791) from the Health and Retirement Study. Cognitive health was measured by a global cognitive function summary score. Social disconnectedness was measured by 3 types of social isolation (from extended family, adult children, and friends) and loneliness (UCLA 3-item Loneliness Scale). Neighborhood contextual factors included neighborhood social cohesion and physical disadvantage. Covariates included age, sex, education, marital status, and living arrangements. We used group-based trajectory modeling to test the study objectives.</p><p><strong>Results: </strong>We identified 4 global cognitive function trajectories: low and declining (14% of sample), moderate and declining (29%), moderate and stable (40%), and high and stable (17%). Multivariable models indicated that neighborhood physical disadvantage (RRR = 0.61, 95% CI [0.40, 0.92]) and social cohesion (RRR = 0.42, 95% CI [0.23, 0.77]) moderated the association between social isolation from extended family and global cognitive function trajectory membership.</p><p><strong>Conclusions: </strong>Our study is among the first to examine cognitive function trajectories with linkages to social disconnectedness and neighborhood contexts among middle-aged and older Black adults. Overall, the results suggest that neighborhood contexts condition how social isolation relates to cognitive trajectories. These findings underscore the importance of considering both social disconnectedness and neighborhood context in explaining heterogeneity in cognitive aging among middle-aged and older Black adults.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993304","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":"Performance of Chronic Conditions Data Warehouse algorithms in Medicare Advantage and fee-for-service populations.","authors":"Chan Mi Park, Xiecheng Chen, Sandra Shi, Lan Luo, Eunji G Kim, Emilie D Duchesneau, Lily Zhong, Dae Hyun Kim, Ellen P McCarthy","doi":"10.1093/gerona/glag230","DOIUrl":"10.1093/gerona/glag230","url":null,"abstract":"<p><strong>Background: </strong>The Centers for Medicare & Medicaid Services (CMS) Chronic Conditions Data Warehouse (CCW) algorithms are widely used to identify chronic conditions in Medicare fee-for-service (FFS) claims. However, their validity in Medicare Advantage (MA) encounters remains uncertain.</p><p><strong>Methods: </strong>We conducted a cross-sectional study using the National Health and Aging Trends Study (NHATS) linked to Medicare data. We analyzed NHATS rounds 9 and 11, aged ≥ 65 years, with continuous 24-month enrollment in MA or FFS. Chronic Conditions Data Warehouse algorithms were applied to identify 6 conditions: arthritis, chronic lung disease, diabetes, heart disease, hypertension, and osteoporosis. Self-reported, physician-diagnosed conditions from NHATS interviews served as the reference standard. Survey-weighted sensitivity, specificity, positive predictive value (PPV), negative predictive value, and balanced accuracy were compared between MA and FFS.</p><p><strong>Results: </strong>We included 1708 MA and 2239 FFS beneficiaries in round 9 and 1472 MA and 1566 FFS beneficiaries in round 11. Across both rounds, balanced accuracy was similar between MA and FFS for all 6 conditions. Diabetes and hypertension demonstrated high sensitivity (0.88-0.94), while arthritis and osteoporosis showed lower sensitivity but high specificity. Although statistically significant MA-FFS differences were observed for select metrics (diabetes PPV in round 9; chronic lung disease specificity in round 11), absolute differences were minor and not clinically meaningful.</p><p><strong>Conclusions: </strong>Chronic Conditions Data Warehouse algorithms perform comparably in MA and FFS Medicare data. These findings support the validity of using CCW algorithms in MA encounter data for epidemiologic research for risk adjustment, facilitating more generalizable studies of the growing MA population.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003293","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":"Effects of resistance training sets on cognition and brain-derived neurotrophic factor in cognitively impaired individuals: a quasi-experimental study.","authors":"Nuno M Fonseca, Dulce Esteves, Diogo L Marques, Carla P Fonseca, Jorge Costa, Tiago Sousa, António C Sousa, Henrique P Neiva, Mikel Izquierdo, Mário C Marques","doi":"10.1093/gerona/glag216","DOIUrl":"10.1093/gerona/glag216","url":null,"abstract":"<p><strong>Background: </strong>The minimum effective resistance training (RT) volume prescription strategy for individuals with cognitive impairment (CI) remains unclear in the literature. This study compared the effects of single-set (SET1) versus three-set (SET3) RT on global cognition, brain-derived neurotrophic factor (BDNF), and physical performance in individuals with CI.</p><p><strong>Methods: </strong>The study was formally registered on ClinicalTrials.gov (NCT06185010; V2) and followed the TREND guidelines. We randomized thirty participants to SET1 (n = 15) or SET3 (n = 15) and nonrandomly allocated thirteen participants to a control group (CON). The 8-week RT program included leg press (40%-60% one-repetition maximum [1RM]), chest press (50%-70% 1RM), chair squats, and med ball throws. Primary outcomes assessed at baseline and post-intervention included the Dementia Rating Scale-2 (DRS-2), serum BDNF, and the Short Physical Performance Battery (SPPB). Secondary outcomes were creatine kinase (CK) and composite strength (handgrip strength plus 1RM leg and chest press). We analyzed the outcomes using generalized linear mixed models.</p><p><strong>Results: </strong>There were no post-intervention between-group differences for DRS-2 or BDNF, and neither group demonstrated increases from baseline. Physical performance improved in both RT groups compared with CON, with SPPB increasing by 2.7 points in SET1 and 1.4 points in SET3. CK did not change meaningfully. Composite strength did not differ between groups at post-test; however, only SET1 showed a significant increase (+12 kg).</p><p><strong>Conclusions: </strong>Both sets improved physical performance but were not associated with detectable changes in cognition or BDNF in individuals with CI. Single sets may represent an efficient strategy in this population.</p><p><strong>Clinical trial registration number: </strong>ClinicalTrials.gov (NCT06185010).</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868703","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":"Wife-husband differences in the associations between sleep durations and global cognition among middle-aged and older married couples in China: a longitudinal dyadic analysis.","authors":"Jie Zhong, Ying Dai, Xiang Qi, Wei Liang","doi":"10.1093/gerona/glag235","DOIUrl":"10.1093/gerona/glag235","url":null,"abstract":"<p><strong>Background: </strong>Sleep duration has well-established U-shaped associations with cognitive health, but research has largely ignored spousal interdependence. This study examined actor and partner effects of sleep duration on global cognition in middle-aged and older Chinese couples, testing whether associations differed by sex.</p><p><strong>Methods: </strong>Data were drawn from CHARLS waves 1-4 (2011-2018). The analytical sample comprised 4260 couples (8520 individuals) aged ≥45 years living in a married, 2-person, mixed-sex household. Global cognition was assessed with a composite battery adapted from the Telephone Interview for Cognitive Status and Chinese Mini-Mental State Examination; nocturnal sleep and napping durations were self-reported. Actor-Partner Interdependence Models with quadratic terms examined actor effects (own sleep predicting own cognition) and partner effects (own sleep predicting spouse's cognition), with false discovery rate (FDR)-adjusted q-values and sex-equality tests.</p><p><strong>Results: </strong>Significant inverted U-shaped actor effects were found for wives (β = -0.010, 95% CI: -0.014, -0.005, p < .001) and husbands (β = -0.011, 95% CI: -0.016, -0.006, p < .001); both survived FDR correction (q = 0.002, q < 0.001). Husbands' sleep was nominally associated with wives' cognition similarly (β = -0.005, p = .025), while wives' sleep was not associated with husbands' cognition (p = .618). The husband-to-wife association did not survive FDR correction (q = 0.239), and sex-equality tests were non-significant (χ²(9) = 9.35, p = .406). Napping showed limited, largely non-significant associations with cognition.</p><p><strong>Conclusions: </strong>Own nocturnal sleep duration shows a robust, symmetric inverted U-shaped association with cognitive function in both spouses. The possible husband-to-wife partner effect did not survive correction for multiple testing and warrants adequately powered investigation before informing couple-based clinical recommendations.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993288","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":"DNA methylation variability provides a complementary epigenetic signature of aging heterogeneity: findings from the Canadian Longitudinal Study on Aging and the Baltimore Longitudinal Study of Aging.","authors":"Olga Vishnyakova, Joosung Min, Ann Z Moore, Toshiko Tanaka, Luigi Ferrucci, Xiaowei Song, Kenneth Rockwood, Angela Brooks-Wilson, Lloyd T Elliott","doi":"10.1093/gerona/glag234","DOIUrl":"10.1093/gerona/glag234","url":null,"abstract":"<p><strong>Background: </strong>Human aging does not follow a single trajectory. Epigenetic changes offer insight into the heterogeneity in aging by reflecting the combined influence of genetic, environmental, and lifestyle factors on the timing and progression of age-related changes beyond what chronological age alone can explain. Recent studies in cancer and aging underscore the importance of methylation variability as a marker of biological dysregulation.</p><p><strong>Methods: </strong>We investigated the role of DNA methylation in aging heterogeneity by performing epigenome-wide differential methylation and variance association analyses in blood samples from 1445 Canadians aged 45 to 85 from the Canadian Longitudinal Study on Aging.</p><p><strong>Results: </strong>We identified 448 differentially methylated regions and 488 differentially variable regions associated with health decline as measured by the health deficit accumulation frailty index, cognitive function, and physical function. These two classes of regions showed minimal overlap, with distinct gene coverage, suggesting that variability contributes a complementary signal to aging heterogeneity. Genes overlapped by differentially methylated regions were enriched for immune and inflammation-related pathways, whereas differentially variable regions highlighted additional localized, CpG‑island-enriched signals shared across health domains, consistent with regionally structured rather than diffuse dysregulation. By integrating significant CpGs from both analyses, we constructed an epigenetic biomarker. The biomarker was associated with all-cause mortality and showed higher discrimination than biomarkers constructed from differential methylation or variability alone, with a similar pattern reproduced in the Baltimore Longitudinal Study of Aging.</p><p><strong>Conclusions: </strong>These findings suggest that DNA methylation variability may provide a complementary dimension of epigenetic aging and support further evaluation in larger cohorts with more mortality events.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993301","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}