Khan SH, Lahue SC, Perkins AJ
… +13 more, Haouili M, Baechle J, Fuentealba M, Jawaid S, Lavadia L, Wang S, Roa Diaz S, Garcia TY, Furman D, Gao S, Boustani MA, Khan B, Newman JC
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41581124
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Epigenetic clocks (ECs) measuring epigenetic age (EA) and epigenetic age acceleration (EAA) are biomarkers of biological aging, but their association with intensive care unit (ICU) delirium remains underexplored. This is...Epigenetic clocks (ECs) measuring epigenetic age (EA) and epigenetic age acceleration (EAA) are biomarkers of biological aging, but their association with intensive care unit (ICU) delirium remains underexplored. This is a pilot study utilizing blood samples from participants enrolled in Pharmacological Management of Delirium. Serum samples were collected within 48 h of ICU admission. DNA isolated from serum clots was analyzed in triplicate for DNA methylation (DNAm). EA and EAA were computed for the Horvath, Hannum, PhenoAge, Horvath Skin & Blood, Telomere Length, Best Linear Unbiased Predictor, Elastic Network (EN), GrimAge1, GrimAge2, and DunedinPACE ECs from DNAm data. Principal-component clocks were also assessed. Coma, delirium, and delirium severity were assessed twice daily. LOS was assessed using electronic medical records. Spearman correlations were computed for relationships between EA/EAA and delirium outcomes using SAS. A convenience sample of 20 ICU patients with delirium was included. Mean age was 66.7 years (SD = 11.3), 12% were female, and 50% were Black. The median delirium/coma-free days (DCFD) by day 8 were 3 (IQR 0, 6.5). The intra-class correlation coefficients for EA ranged from 0.893 to 0.999, indicating good reliability and minimal variability across the replicates. EN EAA was moderately inversely correlated with mean CAM-ICU-7 scores by day 8 (Spearman r = -0.54, p = .01) and discharge (r = -0.48, p = .03). No other correlations between other EA/EAAs and delirium, ICU or hospital LOS reached statistical significance. This pilot study demonstrates the feasibility of using ECs from serum clots. Larger studies are needed to assess the relationship between EA/EAA and delirium.
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41559923
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BACKGROUND: The Frailty Index of Cumulative Deficits (FI-CD) is a key predictor of adverse health outcomes in older adults, but its utility for cross-study comparisons is limited due to assumptions of item homogeneity. M...BACKGROUND: The Frailty Index of Cumulative Deficits (FI-CD) is a key predictor of adverse health outcomes in older adults, but its utility for cross-study comparisons is limited due to assumptions of item homogeneity. METHODS: We constructed a Frailty Index based on Item Response Theory (FI-IRT) in frailty measures, including 51 health-related variables, in older adults from the China Health and Retirement Longitudinal Study (CHARLS) 2011-2020, the Health and Retirement Study (HRS) 2010-2020, and the Survey of Health, Aging, and Retirement in Europe (SHARE) 2010-2020. A two-parameter logistic (2PL) model estimated FI-IRT scores, and Cox/logistic regression assessed its associations with mortality. Several analyses tested its robustness to the variable set and population selection. RESULTS: The FI-IRT followed a slightly right-skewed, approximately normal distribution, with frailty prevalence of 16.3% (CHARLS), 28.5% (HRS), and 15.5% (SHARE). The FI-IRT showed a high level of agreement with the FI-CD, both on a continuous scale and a hierarchical scale. A higher FI-IRT was associated with an increased risk of all-cause mortality across all 3 cohorts (hazard ratios: 1.81-2.38, p < .001). When domain-specific variables were excluded, the FI-IRT continued to offer relatively stable estimations (intraclass correlation coefficient: 0.934; 95% CI, 0.933-0.934; p < .001). A high degree of consistency was observed between the FI-IRTs calculated from models constructed based on different subpopulations (Spearman's rank correlation coefficients: 0.971-0.999, p < .001; intraclass correlation coefficient: 0.945; 95% CI, 0.850-0.972; p < .001). CONCLUSIONS: The FI-IRT provides a useful, robust, and cross-study comparable measure of frailty.
Drewel MA, Schwartz S, Rattinger GB
… +2 more, Buhusi M, Tschanz JT
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41559920
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BACKGROUND: Traumatic brain injury (TBI) is a well-recognized risk factor for late-life cognitive decline. However, few studies have examined individual differences in sex and genetics, which may modify risk. We examined...BACKGROUND: Traumatic brain injury (TBI) is a well-recognized risk factor for late-life cognitive decline. However, few studies have examined individual differences in sex and genetics, which may modify risk. We examined sex differences in gene-TBI interactions for dementia risk genes apolipoprotein E (APOE) and selected brain-derived neurotrophic factor (BDNF) single-nucleotide polymorphisms (SNPs) in predicting late-life cognitive decline. METHODS: We studied 4293 individuals without dementia at baseline (mean age: 74.93, SD: 6.87 years, 57% female). Approximately 25% reported a history of TBI. Linear mixed effects models examined associations between sex, TBI characteristics, APOE genotype, BDNF SNPs and their interactions, with cognitive decline. RESULTS: Compared to males, females experienced fewer TBIs across the lifespan, the majority occurring in late-life. Number of TBI interacted with sex and APOE genotype such that female APOE ε4 allele carriers with multiple TBIs exhibited worse outcomes on global cognition (P < .001; eg, ε4+/TBI2+ estimated marginal means [EMMs] from baseline to year 10 = -17.22 points compared with ε4-/TBI2+ = -7.21), whereas males did not exhibit differential decline by APOE ε4 alleles and TBI number. BDNF Val66Met genotype showed trend-level moderation of TBI history and cognitive decline, with slower decline experienced by heterozygous individuals with multiple TBIs compared with homozygous major allele carriers. There were few significant associations between timing and severity of TBI with cognitive outcomes. CONCLUSIONS: These results underscore the importance of considering individual differences of sex and APOE and BDNF-related gene variants on the long-term cognitive effects of TBI.
Liang Z, Jin W, Liu S
… +6 more, Zhao L, Duan C, Yin Q, Jin J, Huang L, Chen H
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41559917
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BACKGROUND: Obesity exhibits metabolic heterogeneity, but its impact on muscle strength decline remains unclear. METHODS: Based on 7772 participants from the China Health and Retirement Longitudinal Study, individuals we...BACKGROUND: Obesity exhibits metabolic heterogeneity, but its impact on muscle strength decline remains unclear. METHODS: Based on 7772 participants from the China Health and Retirement Longitudinal Study, individuals were classified into 4 body mass index (BMI)-metabolic phenotypes (metabolically healthy normal weight [MHNW], metabolically unhealthy normal weight [MUNW], metabolically healthy overweight/obesity [MHOO], metabolically unhealthy overweight/obesity [MUOO]). Grip strength was used to assess muscle strength, and linear mixed-effects models examined phenotype-specific associations with muscle decline. RESULTS: Baseline muscle strength was significantly lower in the MUOO group compared to MHNW. Longitudinal analysis showed accelerated muscle loss in the MUOO group across low (β = -0.0164), medium (β = -0.0091), and high (β = -0.0159) muscle strength levels (p < .05). Transition analysis showed that participants transitioning from MUOO to MHNW demonstrated an additional annual decrease in muscle strength of 0.0465 (95% confidence interval [CI] = -0.0612 to -0.0318), compared with those maintaining stable MHNW. In the low muscle strength group, the stable MUNW (β = -0.0140), MHOO (β = -0.0195), and MUOO (β = -0.0263) groups all delayed recovery (all p < .05). In the medium muscle strength group, stable MUOO accelerated decline (β = -0.0091, 95% CI: -0.0182 to -0.0000), whereas decline was significantly slowed in those transitioning from MUOO to MUNW (β = 0.0329, 95% CI = 0.0135 to 0.0523). CONCLUSIONS: Both BMI and metabolic status influence muscle strength trajectories. Maintaining normal weight and metabolic health is essential for recovery in low-strength individuals, while weight loss may help mitigate decline in those with medium strength.
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41559914
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BACKGROUND: Age-related muscle loss and obesity are linked to poor bone health and increased fracture risk, though findings in frail populations are inconsistent. This study examined differences in bone microarchitecture...BACKGROUND: Age-related muscle loss and obesity are linked to poor bone health and increased fracture risk, though findings in frail populations are inconsistent. This study examined differences in bone microarchitecture across body composition phenotypes in frail older women. METHODS: In this cross-sectional study, 280 older women were included, 109 of whom met Fried frailty criteria. Body composition was assessed using dual-energy X-ray absorptiometry and classified into four groups: low appendicular lean mass (LALM; <20th percentile of residuals), obesity (fat mass index >13 kg/m²), obesity with LALM, or neither. Bone microarchitecture was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Analyses used generalized estimating equations with Bonferroni correction, χ² tests, and Fisher's exact tests. RESULTS: Compared with the obesity group, women with LALM had smaller cortical area and thinner cortex at both the tibia and radius. At the radius, the LALM group also showed lower cortical area and thickness, total volumetric bone mineral density, and trabecular number, as well as greater trabecular area and separation, compared with the obesity plus LALM group. Bone strength was significantly lower in the LALM group than in the obesity and obesity plus LALM groups. CONCLUSIONS: Among pre-frail and frail older women, obesity was associated with more favorable cortical and trabecular bone microarchitecture compared with low muscle mass without obesity. Excess adiposity may partially mitigate skeletal deterioration. Longitudinal studies are needed to clarify the impact of body composition on fracture risk in frail older adults.
Thompson AC, Abdelfattah LI, Duchesneau ED
… +2 more, Joshi A, Hanchate AD
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41557859
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BACKGROUND: Falls and fractures are a significant public health concern linked to visual impairment. Cataracts are the most common cause of visual impairment in older adults and can be corrected with cataract surgery. Th...BACKGROUND: Falls and fractures are a significant public health concern linked to visual impairment. Cataracts are the most common cause of visual impairment in older adults and can be corrected with cataract surgery. This study evaluated whether cataract surgery reduces the one-year risk of falls/fractures in Medicare beneficiaries with cataract. METHODS: Using 2019-2021 claims data from a nationally representative cohort of 940 233 Medicare fee-for-service enrollees (66+ years), we identified those with untreated cataract in 2019 and grouped them into those with and without cataract surgery in 2020. Using the surgery date (surgery group) or a randomly assigned date in 2020 (non-surgery group) as the index date, we identified incident falls/fractures (outpatient, emergency department, or inpatient) during the following 365 days. We used a propensity score-based (with average treatment effect on the treated weights) linear probability regression model to estimate the association of cataract surgery with the risk (likelihood) of falls/fractures, accounting for observed differences between those with and without surgery. RESULTS: Without surgery, the estimated likelihood of falls/fractures was 8.86% (95% CI, 8.53-9.18%). Cataract surgery was not associated with a significant difference in the risk of falls/fractures (risk difference = -0.15 percentage points; 95% CI, -1.0, 0.74). Similar findings were observed for subgroups by race and ethnicity, frailty, and fall/fracture history. CONCLUSIONS: Cataract surgery was not significantly associated with one-year risk of falls/fractures in Medicare beneficiaries. Future studies should evaluate fall risk over a longer follow-up period or the impact of surgery on self-reported falls not captured by the healthcare system.
Düvenci Birben Ö, Teker HT, Keskin S
… +6 more, Baba B, Koçpınar EF, Yıldırım V, Kabayer S, Külahlıoğlu N, Ceylani T
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41557856
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BACKGROUND: Heterochronic plasma exchange is widely used to investigate systemic aging; however, its pulmonary consequences particularly regarding oxidative stress, antioxidant defense, and tissue architecture have not b...BACKGROUND: Heterochronic plasma exchange is widely used to investigate systemic aging; however, its pulmonary consequences particularly regarding oxidative stress, antioxidant defense, and tissue architecture have not been systematically examined. METHODS: Twenty-four-month-old male Sprague-Dawley rats received 0.5 mL of young plasma intravenously daily for 30 days, while 8-week-old rats received 0.25 mL of aged plasma. After treatment, lung tissues were analyzed histologically, biochemically, and molecularly. RESULTS: Quantitative PCR showed that young plasma markedly upregulated antioxidant defenses, with SOD and CAT expression increasing by ∼2.5-fold and 1.8-fold, respectively (p < 0.01), accompanied by higher SOD and GPX enzyme activities (p < 0.05). Additional antioxidant genes (GR, GST, TXN/TXNR) were also significantly upregulated, confirming a broad activation of the antioxidant network. In contrast, aged plasma suppressed antioxidant responses, reducing CAT activity by ∼35% (p < 0.01) and similarly decreasing other enzymes. Histological analyses revealed preserved alveolar structure, thinner septa, and reduced inflammation in old + young plasma rats, while young + old plasma transfer caused structural deterioration. Immunohistochemistry confirmed increased GPX, SOD, and CAT expression in aged rats receiving young plasma, consistent with transcriptional and protein-level activation. Moreover, heterochronic plasma exchange attenuated collagen accumulation, suggesting reduced fibrillar matrix deposition, and restored the balance between alveolar epithelial Type I (AT1) and Type II (AT2) cells, indicating improved epithelial homeostasis. Toluidine Blue staining showed decreased mast-cell density after young plasma treatment (p < 0.05), reinforcing its anti-inflammatory effect. CONCLUSIONS: Young plasma exerts regenerative and anti-inflammatory actions in the aged lung, highlighting it as a key target of systemic rejuvenation.
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41557837
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BACKGROUND: Long-term exposure to air pollution has been linked to adverse health outcomes in older adults; however, its association with frailty, particularly the potential protective role of environmental factors such...BACKGROUND: Long-term exposure to air pollution has been linked to adverse health outcomes in older adults; however, its association with frailty, particularly the potential protective role of environmental factors such as greenness, remains insufficiently investigated. METHODS: Data from the Healthy Aging Longitudinal Study in Taiwan, which included 5336 community-dwelling individuals aged 55 years and older, were analyzed. Frailty was assessed using modified criteria from the Cardiovascular Health Study. Exposure to air pollutants was estimated using land use regression model with machine learning methods. Greenness was quantified using the normalized difference vegetation index (NDVI). Logistic regression models were used to examine associations between environmental exposures and frailty after adjustment for demographic, health, and lifestyle confounders. RESULTS: Exposure to PM2.5 and NO2 during the 1-9 years preceding the assessment was significantly associated with an increased risk of frailty and prefrailty. Conversely higher NDVI values exhibited a protective effect. Mutually adjusted models confirmed the robustness of the effects of PM2.5, indicating its influence persisted for up to 3 years. The aOR for PM2.5 was 1.103 per 10 µg/m³ increment for 3 year prior to the assessment, corresponding to an excess risk of 10.3% per 10 µg/m³ increase. CONCLUSIONS: Long-term exposure to PM2.5 related to frailty in older adults, whereas greenness provides protective benefits. These findings indicate the importance of developing public health policies aimed at improving air quality and promoting greening in ensuring healthy aging.
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41556115
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There is growing interest in whether adult vaccines such as shingles vaccine may slow biological aging beyond preventing acute infections. Using data from the nationally representative US Health and Retirement Study, we...There is growing interest in whether adult vaccines such as shingles vaccine may slow biological aging beyond preventing acute infections. Using data from the nationally representative US Health and Retirement Study, we examined whether shingles vaccination is associated with more favorable profiles across 7 biological aging domains: inflammation, innate and adaptive immunity, cardiovascular hemodynamics, neurodegeneration, and epigenetic and transcriptomic aging, as well as a composite biological aging score. Analyses included adults aged ≥ 70 in 2016 (n = 3884), with biological measures drawn from venous blood, flow cytometry, and physical assessments. Weighted linear regressions adjusted for sociodemographic and health covariates. Shingles vaccination was significantly associated with lower inflammation scores (b = -0.14, p = .0027), slower epigenetic (b = -0.17, p = .0001) and transcriptomic aging (b = -0.19, p < .0001), and a lower composite biological aging score (b = -0.18, p = .0002), suggesting potential benefits for systemic inflammation, molecular and overall biological aging. In contrast, vaccination was linked to higher adaptive immunity scores (b = 0.09, p = .0133), an unexpected finding warranting further investigation. Timing analyses indicated that epigenetic, transcriptomic and overall composite biological aging improvements were most pronounced within 3 years postvaccination, with slower aging persisting beyond this window. The results support the hypothesis that shingles vaccination may influence key biological systems relevant to aging, though effects appear domain-specific and vary over time. Longitudinal studies are needed to confirm these patterns and explore implications for long-term health. This study adds to emerging evidence that vaccines could play a role in strategies to promote healthy aging by modulating biological systems beyond infection prevention.
Karam Y, Shum LC, Faruk T
… +8 more, Arora T, McArthur C, Chu CH, McGilton KS, Flint AJ, Lim A, Khan SS, Iaboni A
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41537232
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BACKGROUND: Disrupted sleep and circadian rhythms in dementia affect rest-activity patterns and impact quality of life, safety, and caregiver burden. The objective of this study is to extend the application of real-time...BACKGROUND: Disrupted sleep and circadian rhythms in dementia affect rest-activity patterns and impact quality of life, safety, and caregiver burden. The objective of this study is to extend the application of real-time location system (RTLS) technology from nurse call and elopement prevention systems to measuring digital markers and phenotypes of rest-activity in people with advanced dementia in residential care. METHODS: Wrist-worn RTLS devices continuously tracked location for up to 16 weeks in 47 participants (21 women, mean age 80.1 years) on a specialized dementia unit. Distance moved in 15-min windows was used to derive digital markers, including parametric and non-parametric features. Panel and mixed-effect models were used to investigate the relationship between clinical assessments and RTLS-based digital markers and phenotypes of rest-activity rhythm. RESULTS: Higher activity intensity was correlated with increased clinical motor agitation scores, and disrupted rhythmicity and reduced time in bed were associated with difficulty falling sleep and increased nighttime motor agitation. Unsupervised machine learning identified 6 distinct rest-activity phenotypes over 1-week periods. These phenotypes include high time in bed, well-regulated, low stability, severe rhythm disturbance, nighttime active, and a highly active individual. Phenotypes differed by age, cognition, mood disturbance, and functional status. Increased activity intensity, decreased rhythmicity, and less nighttime time in bed were associated with higher motor agitation and sleep disruption. CONCLUSIONS: RTLS-derived rest-activity markers and phenotypes were associated with changes in clinical assessments over time and may support data-driven, evidence-based dementia care.
Trevisan C, Remelli F, Bandinelli S
… +8 more, Corti MC, Sergi G, Atti D, Noale M, Maggi S, Guralnik JM, Ferrucci L, Volpato S
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41533717
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BACKGROUND: Skeletal muscle dysfunction contributes significantly to disability, which is one of the most common complications of diabetes in older adults. We aimed to assess whether diabetes was associated with a steepe...BACKGROUND: Skeletal muscle dysfunction contributes significantly to disability, which is one of the most common complications of diabetes in older adults. We aimed to assess whether diabetes was associated with a steeper muscle strength decline and whether lower strength is related to a higher diabetes incidence in older adults. METHODS: A prospective analysis of data from two Italian population-based studies in older adults (the Invecchiare in Chianti and Progetto Veneto Anziani studies). Diabetes was assessed at baseline and after a median of 4.4 (first follow-up) and 6.3 years (second follow-up) using multiple sources of information. Muscle function was assessed as handgrip strength. RESULTS: The sample comprised 3927 participants (58.6% females) with a mean age of 75.5 years (29.6% aged ≥80 years). After adjusting for potential confounders, the decline in muscle strength among individuals with diabetes exceeded that of those without diabetes by 0.70 kg (95% CI, -1.30 to -0.11) at the first follow-up and by 0.84 kg (95% CI, -1.61 to -0.07) at the second follow-up. In those taking oral antidiabetics, this association was even stronger. Over a median 5-year follow-up, 186 incident diabetes cases were recorded. In a multivariable Cox regression, each 1-SD higher in the handgrip/body weight ratio was associated with an 20% lower likelihood of incident diabetes (95% CI, 0.68-0.95, n = 3102). CONCLUSIONS: These findings demonstrate an independent circular relationship between diabetes and skeletal muscle strength. In older people, muscle dysfunction may be a long-term diabetes complication. Whether increasing muscle strength might reduce diabetes risk remains to be determined.
Tanaka T, Lyu W, Hirano H
… +2 more, Shirobe M, Iijima K
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41533683
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BACKGROUND: Oral frailty may be associated with adverse health outcomes; however, its long-term impact on psychological well-being and cognitive function remains unclear. We aimed to examine the longitudinal association...BACKGROUND: Oral frailty may be associated with adverse health outcomes; however, its long-term impact on psychological well-being and cognitive function remains unclear. We aimed to examine the longitudinal association between oral frailty and trajectories of subjective well-being, depressive symptoms, and cognitive function in community-dwelling older adults. METHODS: We conducted a 12-year prospective cohort study of community-dwelling adults aged ≥65 years in Kashiwa, Japan. Oral frailty was assessed using items corresponding to the Oral Frailty 5-item checklist (OF-5). Outcomes included the World Health Organization-Five Well-Being Index, Geriatric Depression Scale-5, Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI), operationally defined as a screening-based outcome using an MMSE cut-off ≤27. All OF-5 components and outcomes were measured across seven waves (2012-2024). Generalized linear mixed-effects models were used to examine longitudinal associations. RESULTS: A total of 1679 participants (mean age 72.7 ± 5.5 years, 49.5% female) were included.Baseline oral frailty was associated with lower subjective well-being (adjusted β = -0.47; 95% CI: -0.77 to -0.17) and higher depressive symptoms (adjusted β = 0.13; 95% CI: 0.06 to 0.19), while time-varying oral frailty showed consistent concurrent associations with both outcomes. Only baseline oral frailty was associated with an increased risk of MCI (adjusted risk ratio, 1.29; 95% CI: 1.13 to 1.38). CONCLUSIONS: Oral frailty has sustained adverse effects on mental well-being and is associated with an elevated risk of cognitive decline. Oral frailty may represent a potential target for interventions aimed at supporting mental and cognitive health in aging populations.
Chen W, Guo R, Zhang W
… +27 more, Yan Q, Wang X, Chen R, Hu X, Liang J, Xing G, Xu D, Ma X, Chen Q, Sha S, Tao E, Cheng L, Fan S, Liu H, Lu T, Yu H, Su J, Xu J, Qin Y, Liu J, Zhong X, Hu X, Hu X, Zheng W, Hu Z, Kang J, Yang J
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41527291
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Gut microbiota plays a pivotal role in Parkinson's disease (PD) pathogenesis. However, the role of enteric viruses remains underexplored. Here, we reanalyzed publicly available metagenomic datasets from two independent c...Gut microbiota plays a pivotal role in Parkinson's disease (PD) pathogenesis. However, the role of enteric viruses remains underexplored. Here, we reanalyzed publicly available metagenomic datasets from two independent cohorts, including 79 PD patients and 79 controls, to characterize gut virome profiles and explore the potential role of enteric viruses in PD pathogenesis and early diagnosis. Our findings indicate increased richness and diversity of the gut virome in PD, with 640 vOTUs differing in abundance between groups. Notably, Siphoviridae and Myoviridae were more abundant in PD patients. A variety of viruses enriched in PD or healthy subjects (HS) preferentially infect bacterial hosts that produce short-chain fatty acids. Furthermore, specific viral functional orthologs, such as thymidylate synthase (K00560) and integrases (K14059), displayed notable differences in prevalence between PD-enriched and HS-enriched vOTUs. Finally, we constructed a random forest model using the top 22 most significant vOTUs, which achieved an AUC of 0.822, demonstrating strong performance in distinguishing PD patients from healthy controls. This is the first study to characterize the gut virome profile in PD, laying a robust foundation for future investigations into the underlying mechanisms and early diagnosis strategies for PD as well as other neurodegenerative disorders.
Li Y, Steinman MA, Lee SJ
… +7 more, Graham LA, Jing B, Dave C, Liu X, Liu CK, Fung KZ, Odden MC
J Gerontol A Biol Sci Med Sci
· 2026 Jan · PMID 41526007
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BACKGROUND: The Veterans Affairs Frailty Index (VA-FI) has been implemented in subgroups of U.S. Veterans. The objectives were to operationalize the VA-FI in long-term care residents and examine its associations with mor...BACKGROUND: The Veterans Affairs Frailty Index (VA-FI) has been implemented in subgroups of U.S. Veterans. The objectives were to operationalize the VA-FI in long-term care residents and examine its associations with mortality, falls, and fractures. METHODS: This retrospective cohort study included Veterans ≥65 years who stayed ≥90 days in Community Living Centers (CLCs). We calculated the VA-FI by dividing the count of health deficits by 31. We categorized the residents in 4 groups: non/pre-frail, mildly, moderately and severely frail. Mortality, the first events of falls and fractures were examined with a 1-year follow-up. Cox regression and Fine-Gray competing-risk models were fit to assess associations between frailty and outcomes. RESULTS: Among 45 183 CLC residents, 12.2% were non/pre-frail, 24.2%, 28.8%, and 34.8% were mildly, moderately and severely frail. With increasing frailty severity, rates of mortality, falls and fractures ranged respectively from 65.3 to 59.0, 13.1 to 18.8, and 1.9 to 2.2 per 100 person-years. Relative to the non/pre-frail, residents with mild, moderate and severe frailty had lower rates of death (HRs [95% CIs]: 0.88 [0.84-0.92], 0.87 [0.83-0.91], 0.90 [0.85-0.94]), higher rates of falls (SHRs [95% CI]: 1.26 [1.10-1.43], 1.32 [1.17-1.50], 1.29 [1.14-1.46]) and fractures (1.29 [0.92-1.81], 1.47 [1.06-2.04], 1.45 [1.04-2.02]). CONCLUSIONS: Frailty was highly prevalent in Veterans receiving long-term care in CLCs and was associated with higher rates of falls and fractures. Frail residents had a lower rate of mortality compared with their non/pre-frail counterparts. Length of stay, confounded by unobserved factors, and collider bias could potentially serve as explanations for this counterintuitive finding.
Zhong X, Huang Z, Huang B
… +4 more, Cai H, Yao Y, Liu K, Li Y
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41485084
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BACKGROUND: The study aimed to investigate the association between changes in sarcopenia and the risk of dementia, and whether cumulative levels of physical activity (PA) mediate the association of changes in sarcopenia...BACKGROUND: The study aimed to investigate the association between changes in sarcopenia and the risk of dementia, and whether cumulative levels of physical activity (PA) mediate the association of changes in sarcopenia with dementia. METHODS: Our data are from the English Longitudinal Study of Aging (2004-2019). Robust, probable sarcopenia and sarcopenia were assessed according to European Working Group of Sarcopenia in Older People (EWGSOP2) criteria. Kaplan-Meier cumulative risk curves were used to explore the association between changes in sarcopenia and the risk of dementia. Cox proportional hazard models were used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI). Causal mediation analysis was used to assess the mediating effects of cumulative levels of PA. RESULTS: A total of 3610 participants were included in the analysis. At a median follow-up time of 9.83 years, 296 participants developed dementia. Compared with participants with stable robust, participants with robust to probable sarcopenia/sarcopenia had an increased risk of dementia (HR = 1.49, 95% CI = 1.05-2.10); conversely, compared with participants with stable sarcopenia, participants with sarcopenia to probable sarcopenia/robust did not have a reduced risk of dementia (HR = 0.79, 95% CI = 0.51-1.52). The cumulative levels of PA mediate the association with robust to probable sarcopenia/sarcopenia and the risk of dementia with a natural indirect effect HR (95% CI) of 1.06 (1.01-1.13), proportion mediated = 15.4%. CONCLUSIONS: Different changes in sarcopenia were associated with different dementia risks, with continued progression of sarcopenia, increased dementia risk, and cumulative levels of PA mediated the association between the progression of sarcopenia and the risk of dementia.
J Gerontol A Biol Sci Med Sci
· 2026 Feb · PMID 41467745
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BACKGROUND: Serum uric acid (SUA) has been linked to cognitive function, but sex-specific associations remain unclear. Biological differences in SUA levels between sexes, driven by hormonal and renal factors, highlight t...BACKGROUND: Serum uric acid (SUA) has been linked to cognitive function, but sex-specific associations remain unclear. Biological differences in SUA levels between sexes, driven by hormonal and renal factors, highlight the importance of sex-stratified analysis. This study examined the association between SUA levels and changes in cognitive function in older adults. METHODS: A total of 11 411 community-dwelling ASPirin in Reducing Events in the Elderly participants, free from dementia at baseline and with valid SUA measurements, were included. The Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test, and Controlled Oral Word Association Test were used to assess cognition at baseline and over a median follow-up of 9 years. Separate linear mixed-effects regression models in males and females were fitted to assess the associations between SUA levels and change in cognitive function over time. RESULTS: Females in the lowest SUA quintile (Q1) had significant declines in the measure of global cognition (3MS: β ±SE= -0.07 ± 0.03, p = .02) and episodic memory (HVLT-R; delayed recall: β±SE= -0.03 ± 0.01, p = .02) compared to the middle quintiles (Q2-Q4), but the highest SUA quintile (Q5) was not associated with decline. No associations were observed for executive function, verbal fluency, or psychomotor speed. In males, no significant associations between SUA levels and change in cognitive function were observed. CONCLUSION: Low SUA levels were linked to decline in the measure of global cognition and episodic memory among females but not males. High SUA levels were not associated with cognitive decline. Managing SUA levels within the physiological range may support cognitive health, particularly in older females.