Parker ES, Golzarri-Arroyo L, Dickinson S
… +7 more, Henschel B, Becerra-Garcia LE, Mokalla TR, Robertson OC, Thapa DK, Vorland CJ, Allison DB
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41837372
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Clustering effects, such as those introduced by housing animals in shared cages, are often overlooked in preclinical lifespan studies, despite their potential to underestimate variance estimates and inflate Type I error...Clustering effects, such as those introduced by housing animals in shared cages, are often overlooked in preclinical lifespan studies, despite their potential to underestimate variance estimates and inflate Type I error rates, leading to misleading conclusions. This methodological oversight reduces statistical rigor and may undermine the reliability of findings. To address this gap, the current study examines the impact of accounting for a clustering and nesting effect on lifespan analyses by comparing the results of statistical models that both account for and ignore this effect. Using 2019 data from the Interventions Testing Program, a large-scale initiative evaluating the effects of compounds on lifespan in UM-HET3 mice as a case study, we illustrate how different modeling approaches influence statistical estimates and conclusions. The clustering and nesting effect was addressed using linear mixed-effects and Cox frailty models, both of which explicitly account for cage-level dependencies and the nesting of cages within treatment. Comparisons were made between unadjusted lifespan analyses and those incorporating the clustering and nesting adjustment. The results of this case study indicate that properly adjusting for a clustering and nesting effect can change the conclusions drawn from statistical significance tests as compared to unadjusted model approaches, and so it remains best practice to properly account for clustering and nesting to reduce the potential for inflated Type I error rates. These findings highlight the importance of accounting for clustering and nesting in preclinical research to ensure valid and robust statistical inference.
Ackley SF, La Joie R, Caunca M
… +6 more, Mukherjee S, Choi SE, Trittschuh EH, Crane PK, Hayes-Larson E, Alzheimer’s Disease Neuroimaging Initiative
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41837371
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BACKGROUND: Blood-based biomarkers for Alzheimer's disease (AD) pathology are appealing options in large population-based studies due to their low cost, minimal invasiveness, and feasibility of collection in non-clinical...BACKGROUND: Blood-based biomarkers for Alzheimer's disease (AD) pathology are appealing options in large population-based studies due to their low cost, minimal invasiveness, and feasibility of collection in non-clinical settings. Despite these benefits, blood-based biomarkers have lower test-retest reliability than neuroimaging measures like amyloid positron emission tomography (amyloid-PET) Centiloids; trade-offs in power and bias remain unexplored. METHODS: We use data from Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) studies, which include both amyloid-PET and blood-based measures, to assess differences in statistical power, required sample size, and bias when replacing a neuroimaging measure with a blood-based measure. We use simulations parameterized based on these studies to show potential implications of using plasma p-tau 181 or p-tau 217, blood-based AD biomarkers, in place of Centiloids from amyloid-PET, when the biomarker is either the exposure or the outcome in an analysis of interest. RESULTS: We demonstrated that substituting amyloid-PET Centiloids with a blood-based measure of p-tau can substantially reduce power, requiring 1.5-6.5 times the sample size to achieve 80% power compared to amyloid-PET. In addition, using a blood-based biomarker as the exposure can introduce significant regression dilution bias, attenuating estimated associations. CONCLUSIONS: While blood-based biomarkers are lower cost and easier to collect than neuroimaging measures, their use as proxies for AD pathology may introduce substantial methodological challenges, depending on the p-tau isoform. Consideration of the sample sizes they necessitate and their potential for bias is critical for the design and interpretation of studies employing these biomarkers.
Jackson EA, Karvonen-Gutierrez CA, Brooks MM
… +5 more, Strotmeyer E, Lange-Maia BS, Solomon DH, Hood MM, Derby CA
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41837362
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BACKGROUND: Metabolic syndrome (MetSyn) is associated with frailty in older adults, with few data among midlife women. We examined MetSyn, including duration, for associations with the development of prefrailty and frail...BACKGROUND: Metabolic syndrome (MetSyn) is associated with frailty in older adults, with few data among midlife women. We examined MetSyn, including duration, for associations with the development of prefrailty and frailty. METHODS: The Study of Women's Health Across the Nation is a multiethnic, longitudinal cohort study of women aged 42-52 years at the time of enrollment (1996-1997). MetSyn was measured longitudinally, using ATP III criteria, starting at baseline. Pre-frailty and frailty were measured at two later visits (2012/13 and 2015/16) using Fried criteria. Associations of pre-frailty and frailty with prevalent MetSyn, the cumulative number of prior visits with MetSyn, and individual MetSyn criteria were examined using multivariable models. RESULTS: A total of 1769 women were included (mean age 59.7 years, SD 3.3). The adjusted odds ratios (aOR) for having pre-frailty or frailty in women with MetSyn compared to those without were 2.77 (95% CI, 2.19-3.50) and 8.73 (95% CI, 5.89-12.95), respectively. Each additional visit a woman met criteria for MetSyn was associated with a higher odds of pre-frailty and frailty (aOR 1.20; 95% CI: 1.14-1.26, and aOR: 1.41; 95% CI: 1.33-1.50, respectively). Individual MetSyn criteria were also associated with the risk of frailty. CONCLUSIONS: Among women in this multiethnic cohort, MetSyn was common during midlife and strongly associated with future development of pre-frailty and frailty while women were in their early 60s. Measurement of MetSyn during midlife can help identify women at high risk for developing frailty early in the aging process.
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41834140
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Although exercise is well established in alleviating aging-associated skeletal muscle atrophy, the underlying mechanism is not fully understood. Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) ha...Although exercise is well established in alleviating aging-associated skeletal muscle atrophy, the underlying mechanism is not fully understood. Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) has been shown to be a crucial adaptor for inflammation and mitochondrial function; however, little is known about the action of ECSIT in skeletal muscle atrophy. First, the young and middle-aged mice underwent exercise training, and then skeletal muscle atrophy, mitochondrial quality control, and mitochondrial complex in skeletal muscle were detected. Then, we analyzed the Gene Expression Omnibus (GEO) database and performed in vivo experiments to determine the effect of exercise on ECSIT expression. Furthermore, ECSIT was knockdown in myoblasts to examine its effects on muscle atrophy, mitochondrial quality control, and mitochondrial complex. Compared with young mice, middle-aged mice exhibited significant reductions in relative weights of skeletal muscles, grip strength, hang time, and exhaustion exercise performance, while exercise restored these deficits dramatically. Consistently, exercise promoted protein synthesis and inhibited protein degradation in the gastrocnemius of middle-aged mice. Therefore, exercise significantly mitigated skeletal muscle atrophy in middle-aged mice. Concomitantly, exercise alleviated the impaired mitophagy in the gastrocnemius of middle-aged mice. ECSIT expression was elevated in the gastrocnemius of middle-aged mice but was reversed by exercise intervention. Mechanistically, ECSIT knockdown impaired myoblast differentiation, mitochondrial complex, and mitochondrial quality control in myoblasts. Collectively, this study reveals, for the first time, that ECSIT is important for myogenesis by maintaining mitochondrial quality control, thereby facilitating exercise-induced amelioration of skeletal muscle atrophy during aging.
Tao J, Wang Y, Xia X
… +11 more, Li Y, Deng X, Zhang F, Huang J, Liang C, He Q, Zhu Y, Yang K, Yuan J, Wang D, Li X
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41832966
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BACKGROUND: Several studies have investigated the effects of dietary one-carbon metabolism (OCM) nutrients, such as methionine, folate, vitamin B6, and vitamin B12, on Parkinson disease (PD). However, current evidence re...BACKGROUND: Several studies have investigated the effects of dietary one-carbon metabolism (OCM) nutrients, such as methionine, folate, vitamin B6, and vitamin B12, on Parkinson disease (PD). However, current evidence remains insufficient to definitively establish a link between OCM intake, PD incidence, and genetic risk. METHODS: Among 202 171 individuals aged 37 to 73 in the UK Biobank, we assessed dietary OCM nutrient intake via repeated 24‑hour recalls, determined PD incidence via validated International Classification of Diseases, 10th Revision (ICD‑10) codes, and quantified genetic risk with polygenic risk scores. Employing Cox proportional hazards models supplemented by sensitivity analyses, we evaluated the associations and potential interactions among OCM nutrient intake, genetic risk, and PD incidence. RESULTS: Over a median 12.27-year follow-up of 202 171 participants, 1037 incident PD cases occurred. In multivariable-adjusted Cox models, compared with participants in the lowest quartile, those in the highest quartile of methionine, vitamin B6, folate, and vitamin B12 had a lower risk of PD (hazard ratio [HR] [95% confidence interval (CI)] = 0.83 [0.69-1.00], 0.75 [0.62-0.90], 0.71 [0.59-0.85], and 0.79 [0.65-0.94]). Genetically stratified analyses showed folate inversely associated with PD risk in the low-risk group (HR [95% CI] = 0.65 [0.48-0.88]) (p for interaction = .48); vitamin B12 linked to lower risk in the high-risk group (HR [95% CI] = 0.78 [0.63-0.99]) (p for interaction = .83); and vitamin B6 inversely associated across both strata (high-risk HR [95% CI] = 0.77 [0.62-0.97]; low-risk HR [95% CI] = 0.59 [0.44-0.80]) (p for interaction = .08). CONCLUSIONS: Higher OCM nutrient intake might be inversely associated with PD risk. However, evidence regarding the independent contributions of dietary and genetic factors remains inconclusive.
Lynch KM, Bennett EE, Liu C
… +8 more, Stapp EK, Levine DA, Glymour MM, Zimmerman SC, Griswold ME, Odden MC, Lopez OL, Power MC
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41830439
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BACKGROUND: Large-scale dementia ascertainment for research remains challenging. We demonstrate a method to impute dementia status and onset time using data from the Cardiovascular Health Study (CHS). METHODS: We used a...BACKGROUND: Large-scale dementia ascertainment for research remains challenging. We demonstrate a method to impute dementia status and onset time using data from the Cardiovascular Health Study (CHS). METHODS: We used a linear mixed-effects model to estimate individual cognitive trajectories and included the estimates as covariates in an accelerated failure time model used to impute time to incident dementia in the CHS Cognition Study, a sub-study with dementia ascertainment. We calibrated the model in a 60% random sample (n = 2000) of eligible participants with CHS Cognition Study dementia classifications and validated the final model in the remaining 40% sample (n = 1334). We then imputed dementia onset time and dementia status during follow-up in the full CHS sample, including those without (n = 1415) CHS Cognition Study dementia classifications. RESULTS: In the validation sample, relative to the CHS Cognition Study dementia classifications used as the "reference standard," specificity (98.5%), positive predictive value (81.9%), negative predictive value (92.0%), and accuracy (91.3%) were high, while sensitivity was modest (43.8%), with mean imputed onset time ±1.5 years of classified. Performance varied by participant characteristics. Ultimately, 227 (16.0%) of participants without CHS Cognition Study classifications, and 472 (9.9%) of all CHS participants were classified as having dementia according to this approach. CONCLUSIONS: The shared parameter approach can be implemented in samples with existing cognitive data and a validation sample with reference-standard dementia adjudication. We found high overall accuracy and higher specificity than sensitivity, similar to reported performance metrics for algorithmic approaches requiring linkage to administrative data.
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41830155
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BACKGROUND: Studies regarding the integration of various biological aging (BA) markers and their predictive values for long-term mortality risk remain limited, particularly in Asian older adults. We evaluated the associa...BACKGROUND: Studies regarding the integration of various biological aging (BA) markers and their predictive values for long-term mortality risk remain limited, particularly in Asian older adults. We evaluated the associations of multiple BA markers with overall and cause-specific mortality over a 20-year period. METHODS: Data on 4000 older adults (mean age: 72.5 years) were obtained from the Mr. OS and Ms. OS cohort. BA was assessed by the frailty phenotype, clinical deficit-based frailty index (FI), biochemical-enhanced FI (eGFR, homocysteine, hsCRP, 25(OH)-D), and leukocyte telomere length. Mortality was ascertained by the Hong Kong Death Registry. Hazard ratios (HRs) were assessed using Cox and Fine-Gray models and predictive accuracy with Harrell's c-index. RESULTS: Over a median follow-up of 18.25 years, 2446 deaths occurred (CVD: 511, cancer: 644). For overall mortality, the HRs (95% CI) of pre-frail and frail groups were 1.24 (1.13-1.35) and 1.66 (1.39-1.98) compared to the fit. Each SD increase in the clinical or biochemical-enhanced FI was associated with 22% or 23% increased risk of overall mortality (p < .001). Longer telomere length reduced overall mortality risk (HR per SD: 0.93, 95% CI: 0.88-0.99). All BA markers except telomere length were significantly associated with CVD mortality. While all BA markers were not significantly associated with cancer mortality. Frailty-related markers showed added predictive values for both overall and cause-specific mortality, while telomere length was specifically predictive for CVD mortality (C-index improvements: 0.32%-7.90%). CONCLUSIONS: Biological aging is associated with overall and CVD-cause mortality in older Chinese and may support risk stratification and personalized interventions.
Sosnowski DW, Shu C, Hsu HY
… +7 more, Jiang Y, Kathuria A, Piggott DA, Mehta SH, Kirk GD, Maher BS, Sun J
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41830149
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We sought to assess the relationship between HIV infection and disease severity with epigenetic age and to examine the combined association of epigenetic age acceleration and HIV infection with mortality. Participants we...We sought to assess the relationship between HIV infection and disease severity with epigenetic age and to examine the combined association of epigenetic age acceleration and HIV infection with mortality. Participants were drawn from the ALIVE study, a community-based cohort of persons who inject drugs (PWID) in Baltimore, MD, USA. DNA from buffy coat samples was bisulfite-treated and assayed using the Illumina MethylationEPIC BeadChip. Repeated assessment of epigenetic age was indexed using PhenoAge, Horvath age, Hannum age, GrimAge, and DunedinPACE. Annual linkage to the National Death Index-Plus provided mortality data. Linear mixed-effects regressions compared epigenetic age acceleration trajectories. Cox models estimated hazard ratios for all-cause mortality by epigenetic age and HIV status, adjusting for demographics, risk behaviors, estimated cell composition, and ancestry principal components. Among 396 participants (127 with HIV [PWH]) and 3862 person-years of follow-up, the median baseline age was 48.5 years; 89% were Black and 69% male. PWH showed greater epigenetic age acceleration than people without HIV (PWoH), especially those with detectable viremia, low CD4 counts, and low CD4:CD8 ratios. Both HIV and epigenetic age acceleration were independently associated with all-cause mortality. Compared to PWoH without PhenoAge acceleration, PhenoAge acceleration with or without HIV was associated with 3.28 (95% CI: 2.06, 5.02) and 2.12 (95% CI: 1.32, 3.41) times higher mortality hazard, respectively. HIV infection, uncontrolled viremia, and poor immune recovery are linked to epigenetic age acceleration, contributing to mortality risk among PWID, underscoring the need to address molecular aging to mitigate mortality in this population.
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41808487
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BACKGROUND: Frailty and poor self-rated health (SRH) as potential indicators of reduced resilience are associated with all-cause mortality. However, it is lesser known whether these associations are independent of each o...BACKGROUND: Frailty and poor self-rated health (SRH) as potential indicators of reduced resilience are associated with all-cause mortality. However, it is lesser known whether these associations are independent of each other, physical disability or disease burden, and whether SRH remains predictive of mortality among frail older adults. METHODS: We leveraged the National Health and Aging Trends Study of US Medicare beneficiaries, followed annually from 2011 to 2019. Baseline assessments included physical frailty and SRH (excellent/very good, good, or fair/poor). Cox models examined associations with all-cause mortality, adjusting for demographic characteristics and comorbidities. Sensitivity analyses excluded participants with probable or possible dementia at baseline. RESULTS: Of the 7425 participants at baseline, 14% were physically frail, and 25% reported fair/poor SRH. Although frailty was positively correlated with fair/poor SRH, 12% of frail participants reported excellent/very good health, and 6.6% of those with fair/poor SRH were non-frail. Over a median follow-up of 4.3 years, 29% died. Compared to non-frail participants, pre-frailty and frailty were associated with 1.4- and 2.0-fold increased hazard of mortality, respectively, after adjusting for SRH (p < .001); reporting good and fair/poor SRH was associated with 29% and 59% higher hazard of mortality compared to excellent/very good SRH, respectively, after adjusting for frailty (p < .001). Fair/poor SRH was associated with higher mortality among the frail. Sensitivity analyses yielded similar results. CONCLUSION: Physical frailty and SRH, while related, capture distinct aspects of health. Each independently and jointly predicts mortality, with SRH retaining prognostic value in frail individuals. Incorporating both measures may improve risk stratification and guide tailored interventions.
Stephan Y, Sutin AR, Luchetti M
… +2 more, Karakose S, Terracciano A
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41808478
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BACKGROUND: Early-life IQ is a consistent predictor of overall late life health, but its association with the risk of dementia is inconclusive. The present study examined the association between IQ in adolescence and the...BACKGROUND: Early-life IQ is a consistent predictor of overall late life health, but its association with the risk of dementia is inconclusive. The present study examined the association between IQ in adolescence and the risk of all-cause dementia in older adulthood. METHODS: Participants (N = 3498) from the Wisconsin Longitudinal Study completed measures of IQ and demographic factors at about age 18 (1957) and were screened for dementia at about age 81 (2019-2024). Education and history of diabetes, hypertension, and smoking were tested as potential mediators. RESULTS: At the 67 years follow-up assessment, 378 participants (11%) had dementia. Higher IQ at 18 was associated with a lower risk of all-cause dementia (Odds ratio [OR] per one-SD increase in IQ= 0.78; 95% confidence interval [95% CI]= 0.69-0.88) at age 81. The association was similar when adolescent IQ was considered as a categorical variable that contrasted the top versus bottom quartiles (OR = 0.59; 95% CI = 0.43-0.81, p < .01). The association persisted controlling for demographic factors, was partially accounted for by the potential mediators (education, clinical and behavioral covariates), and was not moderated by sex or childhood socioeconomic status. CONCLUSIONS: Adolescent IQ is an early life factor associated with a lower risk of dementia in older adulthood. This research highlights the importance of a life-course perspective on brain health.
Moyes SA, Selak V, Plank LD
… +3 more, Hikaka J, Teh R, Kerse N
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41808475
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BACKGROUND: The number of people losing their independence is increasing as the population ages. Sarcopenia, low muscle strength and mass, and hand grip strength (HGS) are known to predict reduced independence in people...BACKGROUND: The number of people losing their independence is increasing as the population ages. Sarcopenia, low muscle strength and mass, and hand grip strength (HGS) are known to predict reduced independence in people in their seventies. This paper investigates these relationships in New Zealand octogenarians, including Indigenous Māori. METHODS: This study used data from Life and Living in Advanced Age: A Cohort Study in New Zealand (LiLACS NZ), which recruited 421 Māori and 516 non-Māori in 2010-2011. The Nottingham Extended Activities of Daily Living (NEADL) scale measured independence. Participants were classified by ethnicity (Māori or non-Māori) and sex into high, medium or low independence trajectory groups based on their six annual NEADL scores using group-based trajectory modelling. The associations between HGS or probable sarcopenia (a binary measure of HGS) and independence trajectory group (high, medium, low) were tested separately by ethnicity and sex in multinomial logistic regression models. RESULTS: Hand grip strength was inversely associated with low (versus medium) independence trajectory among Māori women, non-Māori women and non-Māori men, adjusting for age, comorbidities and cognition (adjusted odds ratio, aOR, 0.84 (95% CI 0.72, 0.97), 0.86 (0.77, 0.96) and 0.90 (0.81, 0.99), respectively). Similar associations were seen for probable sarcopenia and independence trajectory among those three groups, but the effects did not reach statistical significance. CONCLUSIONS: Hand grip strength could be a valuable screening tool to assess independence trajectory in octogenarians, but further study is needed to clarify the effects of indigeneity and sex in this population.
Stevenson-Hoare J, Stoffel M, Schöttker B
… +4 more, Holleczek B, Zaugg J, Ditzen B, Brenner H
J Gerontol A Biol Sci Med Sci
· 2026 Apr · PMID 41766361
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Individuals who share their environment for long periods of time, that is, spouses, are likely to share behaviors and exposures, and longer spouse-pair cohabitation durations have been suggested to increase methylation p...Individuals who share their environment for long periods of time, that is, spouses, are likely to share behaviors and exposures, and longer spouse-pair cohabitation durations have been suggested to increase methylation pattern similarity on a methylome-wide scale. Risk scores and aging clocks based on blood DNA methylation use subsets of the methylome that share functional associations with disease and phenotype outcomes to estimate exposure and disease-specific epigenetic effects. By using the CpG sites contained within methylation risk scores and aging clocks, it is possible to examine functionally-linked methylation patterns of long-term shared exposure effects. In a population cohort of paired adults, we observed that methylation disease and phenotype risk scores show no significant correlation between partners, and neither do aging clocks after adjustment for age, which is already correlated in pairs. We also did not find evidence of an absolute difference in scores being significantly associated with cohabitation duration. However, when we examined the correlation in normalized methylation values between partners, we observed that correlations were higher in pairs with longer cohabitation durations for many, but not all, functionally-linked CpG sets. This supports the hypothesis that shared cohabitation's association with methylome-wide similarity in pairs is the result of many shared exposures, not a generic effect of cohabitation. Further research is required to establish the precise exposure-methylation links implicated.
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41766355
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BACKGROUND: In animal models, caloric restriction (CR) and time-restricted eating (TRE) extend lifespan and healthspan; however, the long-term benefits in humans are unknown. The goal of the Health, Aging and Later-Life...BACKGROUND: In animal models, caloric restriction (CR) and time-restricted eating (TRE) extend lifespan and healthspan; however, the long-term benefits in humans are unknown. The goal of the Health, Aging and Later-Life Outcomes Pilot (HALLO-P) was to inform the design of a definitive trial to evaluate the long-term effects of CR and TRE in older adults with overweight or obesity. METHODS: HALLO-P randomized 90 older (≥60 years) adults with obesity or overweight to one of three 9-month interventions: (1) 20% CR delivered in-person; (2) 20% CR delivered remotely (RCR); and (3) 8-hour TRE with ad libitum caloric intake. The degree of sustained CR (by doubly labeled water), the sustainability of TRE, participant retention, and changes in body mass and composition, physical performance, and cardiometabolic risk factors were examined. RESULTS: Participants had a mean (SD) age of 67.2 (4.9) years and BMI of 31.7 (2.9) kg/m2; 62% were female and 83% White. Participant retention was 92%. The mean (SD) percent CR was 4.5% (11.0) in CR and 6.0% (10.3) in RCR. TRE participants reported eating within an 8.5-hour window a median of 84% of days. Mean change in body mass was -4.4, -6.7, and -1.0 kg in CR, RCR, and TRE, respectively. CR and RCR lost fat and lean soft tissue. Chair stand and 400-m walk times improved in RCR and TRE, and there were improvements in glucose and cholesterol levels in all 3 groups. CONCLUSIONS: HALLO-P showed that the CR and TRE interventions were feasible and associated with improvements in health status over 9 months despite not achieving the target CR.
Lynch SD, Howard M, Beavers DP
… +6 more, Weaver AA, Lenchik L, Barnard R, Cawthon PM, Bon J, Beavers KM
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41761582
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BACKGROUND: The INVEST in Bone Health Trial examined the effects of weight loss (WL), WL plus resistance training (WL + RT), or WL plus weighted vest use (WL + VEST) on musculoskeletal health. This secondary analysis eva...BACKGROUND: The INVEST in Bone Health Trial examined the effects of weight loss (WL), WL plus resistance training (WL + RT), or WL plus weighted vest use (WL + VEST) on musculoskeletal health. This secondary analysis evaluated changes in muscle area and density using computed tomography (CT) and lean and fat mass using dual-energy x-ray absorptiometry (DXA). METHODS: One hundred fifty participants (50/group) were randomized to 12-months of WL, WL + RT, or WL + VEST, undergoing CT and DXA scans at baseline, six- and 12-months. DXA measured lean and fat mass, while CT assessed muscle and intermuscular adipose tissue (IMAT) cross-sectional area (CSA) and density. Mixed linear models evaluated changes and treatment effects, and partial Pearson's correlations examined relationships between weight change and CT/DXA outcomes. RESULTS: Participants (66.4 ± 4.6 years, 75% female, 69% white) were living with overweight (14.7%) or obesity (85.3%). All groups achieved similar and significant weight loss (∼10%). At 12-months, WL + RT increased mid-thigh muscle CSA (0.5%, p < .05), improved muscle density (3.7%-5.9%, p < .03), and reduced IMAT (20%-22%, p < .05) and fat masses (22%-26.8%, all p < .061). At the trunk, WL + VEST showed a trend toward muscle preservation and improved density (4.2%, p = .08) compared to WL, but had minimal impact on other measures. Differences between WL + VEST and WL were insignificant (all p > .05), but group comparisons showed improvements for WL + RT. Weight loss correlated with increased muscle density (r < 0, p < .001) but reduced muscle CSA and IMAT (r > 0, p < .001), indicating improved quality but reduced quantity. CONCLUSION: Our findings underscore the significance of weight loss-associated muscle loss, highlighting progressive RT as a minimally effective preservation strategy.
Shireman TI, Roma C, Zullo AR
… +6 more, Coe AB, Daiello LA, Liu CJ, Lo D, Bynum JPW, Gerlach LB
J Gerontol A Biol Sci Med Sci
· 2026 Mar · PMID 41761575
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BACKGROUND: Federal policies have successfully targeted the prevalence of antipsychotic (AP) exposure in NHs, but the duration of treatment among nursing home (NH) residents has not been reported. We evaluated AP duratio...BACKGROUND: Federal policies have successfully targeted the prevalence of antipsychotic (AP) exposure in NHs, but the duration of treatment among nursing home (NH) residents has not been reported. We evaluated AP duration and discontinuation within six months in residents with dementia. METHODS: Retrospective cohort study of long-stay NH residents with dementia who newly initiated an AP medication. We evaluated changes in AP duration and discontinuation within six months relative to two federal initiatives: National Partnership to Improve Dementia Care (2012) and inclusion of AP use measures in the NH Star Ratings (2015). We accounted for resident and facility characteristics in a competing-risks analysis establishing the relationship between the two policy periods and AP outcomes. RESULTS: There were 43 668 new episodes of AP initiation among 38 275 residents. The duration of treatment within six months declined from 125.9 days in the pre-Partnership period to 120.5 days and 120.6 days in the post-Partnership and post-Five Star periods, respectively. Those who initiated APs after the Partnership [adjusted hazard ratio (aHR) = 1.17; confidence interval, 1.10-1.24] and after the Five Star Rating change (aHR = 1.19; 95% CI, 1.07-1.32) policy periods were more likely to stop the medication within 6 months as compared to those who initiated during the prior period. CONCLUSIONS: Federal policies designed to reduce AP prescribing in NH residents with dementia had a nominal impact on treatment duration within the first six months, with more than half continuing treatment beyond 6 months.
Sun Q, Hu J, Yu C
… +11 more, Sun D, Pei P, Yang L, Chen Y, Du H, Zhang X, Schmidt D, Chen J, Chen Z, Li L, Lv J
J Gerontol A Biol Sci Med Sci
· 2026 May · PMID 41761476
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BACKGROUND: Little is known about how sleep problems affect total life expectancy (LE) and LE free of cardiovascular disease (CVD) and its subtypes. METHODS: We included 483384 adults from the China Kadoorie Biobank. Sle...BACKGROUND: Little is known about how sleep problems affect total life expectancy (LE) and LE free of cardiovascular disease (CVD) and its subtypes. METHODS: We included 483384 adults from the China Kadoorie Biobank. Sleep duration was categorized as <6 hours per day (h/d), 6-9 h/d, and >9 h/d. Sleep disturbance was defined as having at least one of the following: self-reported difficulties initiating and maintaining sleep, early morning awakening, and daytime dysfunction. We estimated sex-specific LE with and without CVD at age 40 by using multistate Markov models, with separate models specified for total CVD, ischemic heart disease, ischemic stroke, and hemorrhagic stroke as the disease state. RESULTS: During a median follow-up of 12.1 years, we documented 135429 incident CVD events and 48372 deaths. Longer sleep duration (>9 h/d) had the greatest impact on total LE and LE free of CVD and its subtypes, with the impact on total LE greater than that of disease-free LE. At age 40, total LE and LE without CVD were reduced by 2.11 and 1.29 years in men, and 1.37 and 0.43 years in women, respectively. In contrast, sleep disturbance mainly reduced disease-free LE, reducing the proportion of life spent healthy; compared with those without sleep disturbance, men and women had 0.46 and 0.22 years lower total LE, and 0.99 and 1.05 years lower LE without CVD. CONCLUSIONS: Abnormal sleep duration, especially long sleep, and sleep disturbance were linked with lower total LE and LE free of CVD in this Chinese population, highlighting the importance of good sleep habits.