The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences[JOURNAL]
Sun
200 papers
Assessment of multidimensional measures of aging cross-sectionally and longitudinally across the entire adult age span in the United Kingdom.
Wang W, Haworth S, Bao Y … +1 more , Kumari M
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41467741 · Publisher ↗
BACKGROUND: Aging is a complex process, starting early in life, manifesting across a hierarchy of biological bodily domains with heterogeneity by sex and increasing age. Several molecular and organ-level biological aging...
BACKGROUND: Aging is a complex process, starting early in life, manifesting across a hierarchy of biological bodily domains with heterogeneity by sex and increasing age. Several molecular and organ-level biological aging measurements have been developed. Reported associations of these measurements with aging-related functional health status are typically limited to cross-sectional research and studies in old people only. METHODS: Using data from UK Household Longitudinal Study, we examined associations between composite biological aging measures (Biological Health Score and DNA methylation algorithms) and grip strength, cognitive function, Short Form 12-item Survey scores, self-rated health cross-sectionally (up to 13 231 participants), as well as subsequent 12-year trajectories of Short Form 12-item Survey scores and self-rated health (up to 112 915 observations). RESULTS: Accelerated biological aging was found to be associated with worse functioning both cross-sectionally and longitudinally. However, associations can be moderated by sex and age group. For example, longitudinally, Biological Health Score was negatively associated with self-rated health (coefficient = -0.06) with a moderating effect of sex (coefficient = -0.02, p < .05; male = reference) and some age groups (40-52 years: coefficient = -0.04, p < .001; 53-65 years: coefficient = -0.03, p < .01; reference = 16-39 years), but not for the oldest group (66+ years: coefficient = -0.01, p = .34). CONCLUSIONS: We conclude that measures of biological age are associated with individual functioning trajectories across the entire adult age span, and studies should consider sex differences and examine the entire age range to fully capture distinct facets of aging complexity.
Oral health conditions and domain-specific cognitive decline in older adults: evidence from the Baltimore Longitudinal Study of Aging 2005-2024.
Qi X, Tian Q, Luo H … +3 more , Resnick SM, Ferrucci L, Wu B
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41467738 · Full text
BACKGROUND: While associations between poor oral health and cognitive impairment are documented, research on how different oral health conditions relate to specific cognitive measures remains limited. METHODS: Using data...
BACKGROUND: While associations between poor oral health and cognitive impairment are documented, research on how different oral health conditions relate to specific cognitive measures remains limited. METHODS: Using data from 756 Baltimore Longitudinal Study of Aging 2005-2024 participants (mean age = 72.0 years, 52.5% women, 24.2% Black), we investigated the association between the first oral health assessment and subsequent cognitive decline across domains in older adults aged 60+ who were free of cognitive impairment at baseline over an average of 7.7 follow-up. Cognitive function was assessed across language, executive function, attention, memory, and visuospatial ability domains, with domain-specific composite scores calculated using various cognitive tests. Oral health was evaluated for clinically-assessed tooth loss and dental plaque, alongside self-reported periodontal symptoms. Linear mixed-effect models were used to examine the longitudinal associations with cognitive decline, adjusted for socio-demographic and clinical characteristics. RESULTS: After covariates adjustment, more tooth loss was associated with greater declines across all cognitive domains, including language (β = -0.0017; 95% CI = -0.0025, -0.0008), executive function (β = -0.0011; 95% CI = -0.0019, -0.0002), attention (β = -0.0011; 95% CI = -0.0021, -0.0001), memory (β = -0.0018; 95% CI = -0.0030, -0.0005), and visuospatial ability (β = -0.0017; 95% CI = -0.0029, -0.0006). Dental plaque was associated with executive function (β = -0.0165; 95% CI = -0.0276, -0.0054) and memory (β = -0.0279; 95% CI = -0.0444, -0.0115) declines. Presence of periodontal symptoms was only associated with executive function decline (β = -0.0004; 95% CI = -0.0007, -0.0001). CONCLUSIONS: Tooth loss may indicate broader cognitive decline, while other oral health conditions, such as plaque and periodontal symptoms, particularly affect memory or executive function. Future studies are warranted to investigate underlying mechanisms.
Adverse childhood experiences are associated with falling among middle-aged and older adults, US 2023 BRFSS data.
Reyes-Ortiz CA, Payan-Villamizar CM, Campo-Arias A … +7 more , Ocampo-Chaparro JM, Sosa-Sarmiento PV, Horne E, Brito R, Gil-Arana A, Luque JS, Harris CM
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41467735 · Publisher ↗
BACKGROUND: Adverse childhood experiences (ACEs) have detrimental health effects later in life. Our objective was to assess the association between ACEs and falls among middle-aged and older adults in the United States....
BACKGROUND: Adverse childhood experiences (ACEs) have detrimental health effects later in life. Our objective was to assess the association between ACEs and falls among middle-aged and older adults in the United States. METHODS: We used data from 38 437 participants aged 45 to 80 years from the 2023 Behavioral Risk Factor Surveillance System. The outcome was falling during the past 12 months. Adverse childhood experiences included questions about events before age 18, and 2 main domains of abuse (5 questions) and household dysfunction (6 questions), with a total score of 0 to 11, dichotomized as ≥2 ACEs versus 0-1. We assessed the association between ACEs and falling and explored whether risk factors for falling mediate the association between ACEs and falling. RESULTS: Among middle-aged adults (45-64 years), 22.3% had fallen, and 46.4% had ≥2 ACEs. Among older adults (≥65), 27.7% had fallen, and 31.7% had ≥2 ACEs. In multivariate analyses, participants with ≥2 ACEs have increased odds of falling compared to those with 0-1 ACEs among middle-aged (odds ratio [OR] = 1.34) and older adult participants (OR = 1.28). Even one individual ACE question, such as living with anyone who served in prison (among 45-64; OR = 1.43) or being sexually touched (among ≥65; OR = 1.45), has an independent association with falling. People with depression, functional difficulties, multimorbidity, and difficulty remembering exhibited higher proportions (%) for mediation. CONCLUSIONS: Adverse childhood experiences are an additional risk factor for falling among middle-aged and older adults in the United States. Clinicians and public health practitioners should also consider ACEs when exploring determinants for falling across the life course.
Physical activity offsets air pollution-related cognitive decline: a retrospective cohort study based on China Health and Retirement Longitudinal Study.
Yu Z, Jiang Z, Feng Y … +5 more , Ni P, He J, Bao Z, Cui J, Li F
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41467733 · Publisher ↗
BACKGROUND: This study examined whether physical activity (PA) buffers air-pollution-related cognitive decline in middle-aged and older adults, quantified the dose-response relationship, and derived pollution-specific PA...
BACKGROUND: This study examined whether physical activity (PA) buffers air-pollution-related cognitive decline in middle-aged and older adults, quantified the dose-response relationship, and derived pollution-specific PA recommendations. METHODS: Data came from 5 waves (2011-2020) of the China Health and Retirement Longitudinal Study, including 12 196 adults aged ≥45 years. Ambient pollutants were estimated using a high-resolution satellite-based model. Linear mixed-effects models assessed main and interactive effects of PM2.5, PA, and PA × PM2.5 on cognition, stratified by socioeconomic status (SES) and residential setting. Isotemporal substitution and generalized additive models evaluated risk-benefit trade-offs and non-linearities. PA prescriptions were calculated using (PM2.5-25) × 1.316, with values ≤0 set to 0. RESULTS: Higher PM2.5 exposure predicted poorer cognition (β = -.0146, p < .001). PA buffered this effect (interaction β = .0344, p = .001), consistent across SES and residence. Among PM2.5 constituents, sulfate (β = -.0136) and black carbon (BC) (β = -.1059) were harmful. Vigorous PA neutralized the BC effect, while light-to-moderate PA offset the sulfate effect. Isotemporal substitution showed that 13.16 min/day of PA offset the cognitive impact of a 10 µg/m³ increase in PM2.5. Region-specific estimates required 10.92 min/day in Beijing and 4.01 in Shanghai, while Guangdong and Fujian required none. CONCLUSIONS: Sulfate and BC are key drivers of PM2.5-related cognitive decline. Roughly 13 min of daily PA neutralizes the effect of each 10 µg/m³ PM2.5 rise. Light-to-moderate PA is preferable in sulfate-dominated areas, while vigorous PA is more effective in BC-dominated regions.
Cross-sectional and longitudinal associations between testosterone and cognitive performance in older people: results of the Berlin Aging Study II (BASE-II).
Bahr V, Schmid H, Vetter VM … +7 more , Spira D, Drewelies J, Regitz-Zagrosek V, Gerstorf D, Düzel S, Mai K, Demuth I
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41460177 · Publisher ↗
BACKGROUND: Age-related declines in gonadal and cognitive function are commonly observed, but their relationship is still not completely understood. METHODS: 615 men and 607 women from the Berlin Aging Study II aged ≥60 ...
BACKGROUND: Age-related declines in gonadal and cognitive function are commonly observed, but their relationship is still not completely understood. METHODS: 615 men and 607 women from the Berlin Aging Study II aged ≥60 years were analyzed at baseline, of which 308 men and 297 women were re-assessed on average 7.2 years later. Total testosterone (TT) was measured, and free testosterone was estimated using the Vermeulen (FTV), Sartorius (FTS), and Free Androgen Index (FAI) equations. Cognitive performance was assessed using the Digit Symbol Substitution Test (DSST) and latent factor scores established from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Plus test battery representing 4 cognitive domains (verbal memory, visuo-construction, executive functions and processing speed, and verbal fluency). Associations between testosterone measures and cognitive function were analyzed using linear regression. RESULTS: Cross-sectional analyses showed negative associations in women between visuo-construction and TT (β = -.215, p = .010) and FTS (β = -.013, p = .03) as well as between verbal fluency and TT (β = -.189, p = .006), FAI (β = -.062, p = .03), FTS (β = -.013, p = .008), and FTV (β = -.012, p = .01). In men, FAI was positively associated with DSST performance (β = .103, p = .003). Longitudinally, higher FAI and FTV at baseline were associated with a less steep decline in DSST performance in men (β = .066 and .007, both p = .03). In women, declines in FAI and DSST scores were positively associated (β = 1.794, p = .03). CONCLUSIONS: Our findings suggest sex-specific associations between testosterone levels and cognitive function in older adults. Higher testosterone levels were predominantly associated with better DSST performance in men, but with poorer visuo-construction and verbal fluency in women.
Quantifying the population-level impact of insomnia on dementia among older adults in the United States.
Lin Y, Wu F, Wu Y … +3 more , Liu W, Danaei G, Chen R
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41454968 · Publisher ↗
BACKGROUND: Insomnia has been identified as a plausible modifiable risk factor for dementia. Quantifying its population-level impact may inform strategies to reduce dementia risk among older adults in the United States....
BACKGROUND: Insomnia has been identified as a plausible modifiable risk factor for dementia. Quantifying its population-level impact may inform strategies to reduce dementia risk among older adults in the United States. METHODS: We used data from the 2022 National Health and Aging Trends Study (NHATS) to classify insomnia as sleep-onset insomnia, sleep-maintenance insomnia, or both, and to identify probable dementia using established algorithms. We obtained relative risks (RRs) from a published meta-analysis. Using these RRs and NHATS prevalence estimates, we estimated the population attributable fraction (PAF) of dementia cases attributable to insomnia overall and stratified by age and sex. RESULTS: Among 5899 participants (44.7% aged ≥80 years; 57.9% females; 77.9% non-Hispanic White), 28.7% (95% CI: 26.9%, 30.5%) reported insomnia symptoms and 6.6% (95% CI: 5.9%, 7.3%) had probable dementia. The estimated PAF of probable dementia due to any insomnia was 12.5% (95% CI: 1.0%, 25.0%), and it was slightly higher among females (13.1%, 95% CI: 1.0%, 26.1%) than males (11.6%, 95% CI: 0.9%, 23.3%). The highest PAF was observed in the 65-69 age group (14.4%, 95% CI: 1.1%, 27.8%) among females and in the 70-74 age group (12.8%, 95% CI: 0.9%, 25.8%) among males. An estimated 449,069 (95% CI: 35 049, 923 082) dementia cases in 2022 could have been prevented if insomnia were eliminated. CONCLUSIONS: Approximately 13% of dementia cases, almost half a million cases, among US older adults may be attributable to insomnia. Addressing insomnia could be a promising target for dementia prevention efforts in aging populations.
PhenoAge and PhenoAgeAccel do not outperform chronological age in predicting physical performance decline or mortality in community-dwelling older adults.
Iuorio MS, De Vincentis A, Lelli D … +4 more , Bandinelli S, Ferrucci L, Antonelli Incalzi R, Pedone C
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41454958 · Publisher ↗
BACKGROUND: Chronological age inadequately captures interindividual variability in aging-related functional decline. Biological age metrics such as PhenoAge and PhenoAgeAccel, based on clinical biomarkers, have shown ass...
BACKGROUND: Chronological age inadequately captures interindividual variability in aging-related functional decline. Biological age metrics such as PhenoAge and PhenoAgeAccel, based on clinical biomarkers, have shown associations with frailty and mortality in clinical populations, but their utility in predicting physical performance decline in community-dwelling older adults remains uncertain. METHODS: We used data from 979 participants aged ≥65 years in the InCHIANTI (Invecchiare in Chianti) study, with complete baseline biomarker and physical performance data. Associations of standardized (z-scores) chronological age, phenotypic age (PhenoAge), and Phenotypic Age Acceleration (PhenoAgeAccel) with longitudinal changes in physical function (rescaled SPPB [rSPPB], continuous rescaled Short Physical Performance Battery) and 10-year all-cause mortality were analyzed using linear mixed and Cox models, respectively. A secondary analysis in 504 participants with normal baseline physical performance (Short Physical Performance Battery [SPPB] ≥ 10) assessed the predictive value of each rescaled metric for the onset of compromised function (SPPB ≤ 9) at 6 years. Model performance was evaluated using Akaike information criterion (AIC) and area under the receiver operating characteristic curve (AUC). RESULTS: All 3 metrics showed statistically significant positive associations with physical function decline and mortality. Chronological age showed the strongest associations with rSPPB decline (β = -0.41, AIC = 3793) and mortality (hazard ratio [HR] = 2.78). PhenoAge (β = -0. 32, AIC = 4338, HR = 2.57) and PhenoAgeAccel (β = -0.14, AIC = 4642, HR = 1.71) showed weaker effects. Chronological age also outperformed PhenoAge and PhenoAgeAccel in predicting SPPB decline (AUC = 0.71 vs 0.69 and 0.55, respectively). CONCLUSION: While PhenoAge and PhenoAgeAccel are associated with adverse functional outcomes, they do not outperform chronological age in a general older population.
Association of cumulative deficit frailty with brain age and Alzheimer's disease-related brain structure starting in late-middle age.
Hunt JFV, Buchholz EJ, Franz CE … +14 more , Reynolds CA, Panizzon MS, Williams ME, Bell TR, Tang R, Hagler DJ, Gillespie N, Elman JA, Neale MC, Dorros S, Dale AM, Kremen WS, Fennema-Notestine C, Vietnam Era Twin Study of Aging
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41429579 · Full text
BACKGROUND: Cumulative deficit frailty (CDF) is a syndrome characterized by the accumulation of negative physical, functional and psychosocial insults. Accumulation of CDF and changes in brain structure both occur during...
BACKGROUND: Cumulative deficit frailty (CDF) is a syndrome characterized by the accumulation of negative physical, functional and psychosocial insults. Accumulation of CDF and changes in brain structure both occur during the transition to older age and are associated with the development of Alzheimer's disease (AD) and related dementias. However, how these phenomena are temporally related to each other during the aging process is not well understood. METHODS: We examined bidirectional relationships between CDF and brain structure using structural MRI-based brain-predicted age difference and an AD brain signature. Longitudinal MRI and questionnaire-based data were collected from men in the Vietnam Era Twin Study of Aging at three study waves (average ages 56, 62, and 68). RESULTS: Best-fitting longitudinal random intercepts cross-lagged panel models support the strong overall association between CDF and brain structural integrity with significant covariance between random intercepts for CDF and brain-predicted age difference (r = 0.36, p < .001) and between CDF and AD brain signature (r = -0.16, p = .005) after controlling for chronological age, smoking, race/ethnicity, and education. Significant bidirectional negative cross-lagged associations suggested attenuation over time of the association between CDF and nonspecific brain aging (βs = -0.33 to -0.23, p ≤ .012) but not between CDF and AD brain signature. CONCLUSIONS: CDF was associated with age-related brain structure via strong time-invariant common variance as well as weaker across-time factors. By contrast, the association between CDF and AD-related brain structure was via moderate common variance and was not temporally dynamic. Together, this suggests that CDF is differentially associated with age-related and AD-related brain changes and may be a clinically relevant risk factor for pathological brain aging.
The Sixth Annual Symposium of the Midwest Aging Consortium.
Sturmlechner I, Ashiqueali SA, Martini H … +50 more , Valdivieso K, Franco AC, Guthikonda P, Dosch AJ, Prieto LI, Asmussen NC, Latham AS, Redden JT, Leitschuh EA, Mashek DG, Passos JF, Rodriguez-Lopez J, Monroe TB, Bernlohr DA, Robbins PD, Knopf BA, Lamming DW, Johnston MJ, Brown-Borg HM, Tye SA, Rhoads TW, Gate DM, Childs BG, Baker DJ, Li X, Jang IH, Camell CD, Miller Z, Phatnani H, Konopka AR, Haak AJ, Vanegas-Avendano N, Akula RN, Limkar AR, Ricke WA, Leiser SF, Correia J, Bai H, Olszewski S, Seldeen KL, Budinger GRS, Morales-Nebreda LC, Winter DR, McCrady-Spitzer SK, Anderson RM, Mihaylova MM, Rojas M, Mora AL, LeBrasseur NK, Schafer MJ
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41429578 · Full text
Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventio...
Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventions. Since its inception in 2019, the Midwest Aging Consortium (MAC) has provided an engaging platform for aging researchers in the United States' Midwest to connect, collaborate, and exchange ideas. The Sixth Annual Research Symposium of the MAC held at the Mayo Clinic in Rochester, Minnesota, in April 2025 highlighted the continued impact of the MAC in bringing together aging researchers, including many trainees and early career investigators, into a collaborative environment. This record-setting event featured interdisciplinary research on key aging mechanisms, including lipid metabolism, mitochondrial dysfunction, stress response, cellular senescence, and immune adaptations across organ systems. New therapeutic concepts and clinical trial approaches were presented. Cutting-edge methodologies including single-cell and spatial transcriptomics, metabolomics, and organoid cultures, to dissect aging process in tissue-specific and systemic contexts also were presented. Overall, the MAC symposium underscored the translational potential of geroscience and reinforced the MAC's mission to accelerate aging research through regional collaborations and innovation.
Dogs and humans share biomarkers of mortality.
Harrison BR, Akey JM, Snyder-Mackler N … +4 more , Raftery D, Creevy KE, Promislow DEL, DAP Consortium
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41429575 · Full text
There is growing interest in the use of molecular features as predictors of age, age-related disease risk and mortality. A major shortcoming of this field, however, is the lack of suitable translational research models t...
There is growing interest in the use of molecular features as predictors of age, age-related disease risk and mortality. A major shortcoming of this field, however, is the lack of suitable translational research models to identify and understand the underlying mechanisms of these predictive biomarkers in human populations. In particular, we lack a system which, like humans, is genetically variable, lives in diverse environments, and experiences age-related chronic conditions treated in the context of a sophisticated health care system. Here, we present results from our analysis of data from the Dog Aging Project (DAP), a long-term longitudinal study of aging in companion dogs. Using longitudinal survival models on data from 937 dogs of the deeply phenotyped Precision Cohort within the DAP, we present the striking finding of a strong, highly significant positive correlation between the effect of individual metabolites on all-cause mortality in humans, and the association of those same metabolites on all-cause mortality in dogs. We also find that across these independent human studies, the biomarkers identified are also highly correlated, strongly suggesting a general signature of mortality within the plasma metabolome across humans, and now in dogs as well. Given the many similarities between dogs and humans with respect to genetics, environment, disease, and disease treatment, and the fact that dogs are so much shorter lived than humans, we argue that dogs represent an extremely valuable translational model in our ongoing effort to understand the underlying molecular causes and consequences of age-related morbidity and mortality in humans.
Pain prevalence and pain management at the end of life: regional and urban-rural differences from a national-representative survey of Chinese older adults.
Pei Y, Qi X, Zhou Z … +4 more , Lou Y, Wang J, Li Y, Wu B
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41429569 · Full text
BACKGROUND: Effective pain management is essential for improving quality of life at the end of life. However, challenges persist globally, particularly in China, where palliative care remains underdeveloped. This study i...
BACKGROUND: Effective pain management is essential for improving quality of life at the end of life. However, challenges persist globally, particularly in China, where palliative care remains underdeveloped. This study investigates pain prevalence and the associations between pain severity, place of death, and the quality of pain management among older adults in China, with a focus on regional and urban-rural disparities. METHODS: We used data from the 2014, 2016, 2018, and 2020 waves of the China Longitudinal Aging Social Survey. The final sample included 1,525 older adults who died during the study period. We conducted OLS regression analyses to examine the regional and rural-urban disparities in the associations between pain severity, place of death, and the quality of pain management. RESULTS: Severe pain at the end of life was reported for 42.6% of decedents. Severe pain and hospital death were associated with better quality of pain management. The association between hospital death and pain management quality was stronger in the Eastern region than in the Middle and Western regions. The associations between severe pain symptoms, place of death, and pain management quality were stronger in urban areas than in rural areas. The urban-rural disparities in pain management quality were stronger in the Eastern region than in the Middle and Western regions. CONCLUSIONS: The regional and urban-rural disparities in end-of-life pain management in China highlight the urgent need to strengthen palliative care capacity in underresourced and rural areas through equitable expansion of home- and community-based services and integrated medical insurance reforms.
Association of neurodevelopmental conditions with Alzheimer's disease and related dementias and Parkinson's disease.
Rast JE, Rosso AL, James BD … +17 more , Underwood JFG, Bergstedt J, Ahlqvist VH, Grove J, Fang F, Goldstein ND, Vivanti G, Levine SZ, Nordström A, Schendel D, Lyall K, Nordström P, Ballin M, Stafford J, Naj AC, Lee BK, LEGENNDS Consortium
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41429566 · Full text
BACKGROUND: Neurodevelopmental conditions (NDC), including attention deficit/hyperactivity disorder (ADHD) and autism, are associated with increased rates of neurodegenerative diseases, including Alzheimer's disease and...
BACKGROUND: Neurodevelopmental conditions (NDC), including attention deficit/hyperactivity disorder (ADHD) and autism, are associated with increased rates of neurodegenerative diseases, including Alzheimer's disease and related dementias (ADRD) and Parkinson's disease. Such associations are unstudied in diverse populations and while controlling for a range of important covariates. The purpose of this study was to examine the association of ADRD and Parkinson's disease with NDCs in a diverse sample of adults. METHODS: This case-control study used data from the United States All of Us Research Program 2018-2023 from approximately 600 000 adults in the United States. We matched on ADRD and Parkinson's disease status to examine the association of these conditions with NDCs. RESULTS: NDC was more prevalent in ADRD cases than in non-ADRD controls (7.8% vs 2.4%) and among Parkinson's disease cases than non-Parkinson's disease controls (4.5% vs 1.8%). After adjustment for sex, age, education level, body mass index, cardiometabolic conditions, and psychiatric conditions, individuals with ADRD had significantly higher odds of having an NDC compared with controls (adjusted odds ratio, 2.68; 95% CI, 2.40-2.99). Similarly, Parkinson's disease cases had 2.09 times the odds of having an NDC as non-Parkinson's disease controls (95% CI 1.66, 2.59) in adjusted models. CONCLUSIONS: As the population of individuals with NDCs ages, and more older adults find themselves in the care of clinicians with expertise in ADRD and Parkinson's disease, it is imperative to understand the support needs of this population, and to provide targets for reducing ADRD prevalence in younger or middle adulthood.
ICEBERG emergency room screening tool for early adverse outcome prediction in older patients admitted to acute care: a multicenter study.
Bischoff-Ferrari HA, Tsai DH, Kistler-Fischbacher M … +15 more , Orav EJ, Lanz P, Geiling K, Klaghofer C, Sidler P, Can U, Steiner R, Minder M, von Rickenbach B, Yildirim-Aman A, Bruppacher H, Dietrich M, Egli A, Gagesch M, Freystaetter G
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41400835 · Publisher ↗
BACKGROUND: The ICEBERG tool was initially validated in two small pilot studies to address the lack of a comprehensive geriatric screening tool in emergency settings. The present study builds on the second pilot study an...
BACKGROUND: The ICEBERG tool was initially validated in two small pilot studies to address the lack of a comprehensive geriatric screening tool in emergency settings. The present study builds on the second pilot study and extends it to a larger, multicenter sample. METHODS: We report results from a large ICEBERG tool validation study across three emergency rooms (ERs) including 1664 patients aged 70 years and older. The tool targets 9 domains and is administered by ER physicians or specialized nurses. To assess criterion validity-the extent to which ICEBERG scores are associated with relevant clinical outcomes-we compared patients who scored below versus above the median (<10; ≥10) ICEBERG score for six key clinical outcomes: length of stay in acute care, nursing care in minutes, one-on-one nursing care, in-hospital mortality, discharge to nursing home, and readmission within 30 days. Negative binomial regression was used for the outcomes length of stay and nursing care in minutes. Logistic regression was used for the other outcomes. All analyses were adjusted for age and sex. RESULTS: Patients with ICEBERG scores of 10 or higher had significantly longer stays in acute care (8.9 vs 6.6 days), required more nursing care (56.4 vs 32.8 h), had higher odds of one-on-one nursing care (Odds Ratio, OR = 2.85), in-hospital mortality (OR = 1.89), discharge to a nursing home (OR = 3.20), or being readmitted within 30 days (OR = 1.81). CONCLUSIONS: Based on our findings, the ICEBERG tool identifies older patients with a geriatric risk profile at ERs on all key clinical outcomes tested.
Impact of multidomain lifestyle intervention on dynamics of cognitive frailty: post hoc analysis of the FINGER trial.
Pöyhönen J, Roitto HM, Lehtisalo J … +9 more , Levälahti E, Strandberg T, Kivipelto M, Kulmala J, Antikainen R, Soininen H, Tuomilehto J, Laatikainen T, Ngandu T
J Gerontol A Biol Sci Med Sci · 2026 Jan · PMID 41397903 · Full text
BACKGROUND: Cognitive frailty (CF), a condition with physical frailty and mild cognitive impairment (MCI) without dementia, is potentially reversible and linked to adverse outcomes. We aimed to investigate the impact of...
BACKGROUND: Cognitive frailty (CF), a condition with physical frailty and mild cognitive impairment (MCI) without dementia, is potentially reversible and linked to adverse outcomes. We aimed to investigate the impact of a multidomain lifestyle intervention on temporal dynamics of CF in older adults at risk of dementia. METHODS: In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), 1259 participants, aged 60-77, were randomized to a 2-year multidomain lifestyle intervention or standard health advice. Frailty was defined by the modified Fried phenotype, and MCI by the lowest quintile in the neuropsychological test battery z score. Having pre-frailty/frailty and MCI was classified as CF. Transition probabilities and predictiveness of CF by 4 different baseline groups (healthy, MCI, pre-frail/frail, CF) were examined using multinomial logistic regression. RESULTS: At baseline, 219 participants (18%) had CF. The risk for developing CF at 2 years was higher in the control group (risk ratio [RR], 1.88, p = .003). The intervention effect was not modified by baseline CF (p = .493). Reversal from CF to no-CF group was more likely in the intervention group, and progression to or persisting with CF was more likely in the control group. Compared with healthy participants (n = 401) at baseline, the MCI group (n = 244) had an RR of 5.10, pre-frail/frail (n = 336) of 3.06, and CF of 30.61 for having CF at 2 years, with no difference between MCI and pre-frail/frail groups (p = .116). CONCLUSIONS: The 2-year multidomain lifestyle intervention was effective in preventing and reversing CF. Participants with MCI or pre-frailty/frailty were both at increased risk for CF compared with healthy participants.
Associations between the triglyceride glucose-body roundness index and frailty trajectory in populations with cardiovascular-kidney-metabolic syndrome: a nationwide prospective cohort study.
Fu Z, Song S, Ji Y … +8 more , Duan L, Wang Z, Chen Y, Guo Y, Zhao K, Xu X, Wang C, Xu Q
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41389335 · Publisher ↗
BACKGROUND: Frailty is a key intervention target for older adults with cardiovascular-kidney-metabolic (CKM) syndrome. Evidence suggests that the triglyceride glucose (TyG) index and body roundness index (BRI) are associ...
BACKGROUND: Frailty is a key intervention target for older adults with cardiovascular-kidney-metabolic (CKM) syndrome. Evidence suggests that the triglyceride glucose (TyG) index and body roundness index (BRI) are associated with frailty; however, the predictive value of their combination (TyG-BRI) remains unclear. METHODS: We analyzed data from 3687 middle-aged and older adults with CKM syndrome in the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020). The frailty index serving as the outcome variable was constructed based on 30 multidimensional health deficit items. The primary exposure, the TyG-BRI index, was calculated as the product of the TyG index and the BRI. Latent growth mixture modeling was employed to identify frailty trajectories. Multivariable adjusted logistic regression was conducted to explore the association between TyG-BRI and frailty trajectories. Subgroup analyses were performed to elucidate the interactions among these factors further. RESULTS: Three distinct frailty trajectories emerged: pre-frailty to frailty deterioration (18.8%), persistent frailty (53.7%), and pre-frailty transition to health (27.4%). The highest TyG-BRI quartile was associated with a higher risk of pre-frailty to frailty deterioration than the lowest quartile (OR = 2.229, 95% CI, 1.137-4.367). Subgroup analysis indicated a significant interaction between age and the association of TyG-BRI with frailty trajectories (p = .041), suggesting the need for age-specific intervention strategies. CONCLUSIONS: The TyG-BRI may be an early metabolic biomarker for pre-frailty to frailty deterioration in individuals with CKM syndrome, particularly in older adults. These findings suggest a critical intervention window targeting metabolic dysregulation during the pre-frailty stage.
Associations between osteosarcopenia and cognitive function in community-dwelling older adults: evidence from a US cohort.
Prokopidis K, Cacciatore S, Kirk B … +3 more , Veronese N, Duque G, Schlögl M
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41389334 · Publisher ↗
BACKGROUND: This study investigated domain-specific associations between osteosarcopenia, defined as the coexistence of osteopenia or osteoporosis with low handgrip strength (HGS), and cognitive function in a cohort of o...
BACKGROUND: This study investigated domain-specific associations between osteosarcopenia, defined as the coexistence of osteopenia or osteoporosis with low handgrip strength (HGS), and cognitive function in a cohort of older adults (≥65 years) from the 2011 to 2014 cycles of the National Health and Nutrition Examination Survey (NHANES). METHODS: Osteosarcopenia was defined by the presence of osteopenia or osteoporosis (based on femoral T-scores) combined with low HGS. Cognitive function was assessed using the Digit Symbol Substitution, Delayed Recall, Intrusion Word Count, and Animal Fluency tests. Linear regression models examined the bidirectional associations between osteosarcopenia and cognitive performance. RESULTS: The sample included 1355 older adults (mean age 70.3 ± 6.9 years; 57% women). Compared to participants with osteoporosis alone, those with coexisting osteoporosis and low HGS performed significantly worse on the Digit Symbol Test (β = -9.6; 95% CI, -16.7 to -2.5; p = .01) and had similar Delayed Recall scores (β = -0.6; 95% CI, -1.3 to 0.1; p = .10). In participants with osteopenia and low HGS, a significant association was observed only for the Digit Symbol Test (β = -8.1; 95% CI, -13.4 to -2.7; p < .01). No significant associations were found for osteoporosis or osteopenia in isolation. CONCLUSIONS: Osteosarcopenia, particularly the combination of reduced bone mineral density and low muscle strength, is associated with poorer performance in selected cognitive domains, especially processing speed and memory. These findings underscore the potential value of integrated screening approaches and multidimensional interventions targeting musculoskeletal and cognitive health in aging populations.
The nonlinear U-shaped association between vitamin D deficiency and biological aging acceleration is enhanced in individuals with higher inflammation levels.
Kositsawat J, Kuchel GA, Zhong K … +3 more , Zhao S, Fortinsky RH, Kuo CL
J Gerontol A Biol Sci Med Sci · 2026 Jan · PMID 41389333 · Publisher ↗
BACKGROUND: Aging is multifactorial, yet aging research emphasizes independent risk factors. Endocrine and inflammatory factors have been linked to opposing and synergistic associations with suboptimal aging. METHODS: Gi...
BACKGROUND: Aging is multifactorial, yet aging research emphasizes independent risk factors. Endocrine and inflammatory factors have been linked to opposing and synergistic associations with suboptimal aging. METHODS: Given the importance of multifactorial nonlinear approaches, we interrogated interactions of vitamin D deficiency (VDD; 25-hydroxyvitamin D (25(OH)D) <20 ng/mL) and high C-reactive protein (CRP) levels (≥2.6 mg/L; the third quartile among the included sample) with biological aging acceleration (BAA) in 313 444 UK Biobank participants. Biological aging acceleration (chronological < expected BA) was derived from PhenoAgeAccel (phenotypic age [PhenoAge] adjusted for chronological age and covariates). 25(OH)D and CRP levels were linked to BAA using restricted cubic spline regression models. RESULTS: We observed moderation effects of CRP on VDD-BAA association, and that of 25(OH)D on the high CRP-BAA association. PhenoAgeAccel values for participants with VDD were 0.576 (95% CI, 0.570-0.583) years at CRP z-score 2, compared to 0.121 (95% CI, 0.120-0.122) years at a CRP z-score of 0. In contrast to a U-shaped relationship between 25(OH)D and BAA, all higher CRP levels were more strongly associated with higher BAA. The association between VDD and BAA was greater in participants with higher CRP levels, yet participants with high CRP levels showed similar BAA regardless of vitamin D levels. CONCLUSIONS: Our findings illustrate these risk factors' nonlinear and interactive nature, highlighting the importance of targeting resulting heterogeneity in aging trajectories by developing more targeted interventions via Precision Gerontology. Approaches may include interventions targeting inflammation in individuals with both VDD and inflammation.
Insomnia symptoms, sleep duration, and risk of falls in older adult women: findings from the Study of Women's Health Across the Nation.
Baker JS, Hood MM, Swanson LM … +5 more , Kline CE, Ylitalo KR, Cauley JA, Green RR, Karvonen-Gutierrez CA
J Gerontol A Biol Sci Med Sci · 2026 Jan · PMID 41389332 · Full text
BACKGROUND: As the leading cause of injury and injury-related death for older adults in the United States, falls can be consequential for function and mortality but are preventable. Sleep may be a modifiable risk factor...
BACKGROUND: As the leading cause of injury and injury-related death for older adults in the United States, falls can be consequential for function and mortality but are preventable. Sleep may be a modifiable risk factor for falls. METHODS: Data from 1795 female participants of the Study of Women's Health Across the Nation (SWAN) were analyzed to examine whether frequent insomnia symptoms and shorter sleep duration are associated with an increased risk of falls or fall burden. At visit 12, assessed insomnia symptoms included frequency of restless sleep, trouble falling asleep, and waking early. Sleep duration was self-reported hours of sleep, dichotomized as fewer than <6 h/night and ≥6 h/night. At visit 15, participants reported the falls in the year prior. Log-binomial and multinomial logistic regression models were adjusted for demographic, health, and socioeconomic factors. RESULTS: Women who reported frequent (5+ times/week) trouble falling asleep and frequent waking at baseline had a 30% increased risk (aRR = 1.30, 95% CI, 1.04-1.62) and 24% increased risk (aRR = 1.24, 95% CI, 1.03-1.49), respectively, of having fallen in the year prior at follow-up. Frequent trouble falling asleep and short sleep duration (<6 h) were both associated with higher odds of falling 3 or more times vs once or never prior to follow-up (aOR = 2.42, 95% CI, 1.26-4.63; aOR = 1.77, 95% CI, 1.08-2.93), respectively. CONCLUSIONS: Multiple indicators of poor sleep, including trouble falling asleep, frequent waking, and short sleep duration, were associated with an increased risk of falling and odds of higher fall burden in older adult women. Promoting adequate, high-quality sleep may be an essential component in fall prevention.
High-fat diet exacerbates skeletal muscle mass loss via Nrf2/Prdx6 pathway in sarcopenic obesity mice.
Wang D, Zheng X, Yang Z … +3 more , Zhang W, Liu S, Niu Y
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41389283 · Publisher ↗
Sarcopenic obesity (SO), a dual condition characterized by the coexistence of sarcopenia and obesity, elevates the risk of metabolic disorders, disability, and mortality to magnitudes exceeding the combined risks of both...
Sarcopenic obesity (SO), a dual condition characterized by the coexistence of sarcopenia and obesity, elevates the risk of metabolic disorders, disability, and mortality to magnitudes exceeding the combined risks of both conditions individually, demonstrating a "super-additive impairment" effect on health. Therefore, this study aims to investigate the mechanisms underlying the pathogenesis and progression of SO. We utilized natural aging mice fed high-fat diets (HFD) to simulate the progression of muscle mass decline observed in geriatric populations and high-calorie diets prevalent in modern societies, creating an SO animal model with exceptional clinical relevance. Our study demonstrates that HFD exacerbates age-related reductions in muscle mass, accompanied by decreased physical performance and increased lipid accumulation. Importantly, HFD-induced lipid infiltration emerges as a significant contributor to the further decline in skeletal muscle mass in SO mice, and the Nrf2/Prdx6 pathway is a mechanism regulating this factor. Aerobic exercise, a safe and reliable means for older adults, is particularly effective for fat loss and muscle maintenance. In our study, aerobic exercise effectively alleviated the detrimental effects of HFD on muscle health in aging mice. Mechanistic studies revealed that Nrf2 and Prdx6 protein expression was significantly suppressed in vivo by HFD and in vitro following palmitic acid (PA) exposure. Conversely, overexpression of Nrf2 and Prdx6 in vitro was able to mimic the protective effects of aerobic exercise. Our results indicate that the Nrf2/Prdx6 pathway plays a crucial role in counteracting muscle mass loss induced by HFD and may underlie beneficial effects of aerobic exercise on skeletal muscle.
Personality traits influence frailty in older adults through health behaviors and psychosocial resources.
Cracas SV, Kenny RA, Scarlett S … +1 more , McCrory C
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41389217 · Publisher ↗
BACKGROUND: Frailty is a critical public health issue in aging populations, linked to increased disability, hospitalization, and mortality. While biological and clinical risk factors are well established, less is known a...
BACKGROUND: Frailty is a critical public health issue in aging populations, linked to increased disability, hospitalization, and mortality. While biological and clinical risk factors are well established, less is known about how psychological traits, particularly personality, influence frailty development and "get outside the skin" to affect health. METHODS: Using data from Wave 3 (2014-2015) of The Irish Longitudinal Study on Ageing (TILDA), we examined associations between the Big Five personality traits and frailty among 2146 community-dwelling older adults. Personality was assessed with the 60-item NEO-FFI-R. Frailty was measured both subjectively (self-reported deficits) and objectively with clinical and functional indicators matched to the subjective items to minimize reporting bias. Mediation analyses explored psychosocial and behavioral pathways, including stress, social support, resilience, smoking, and body composition. RESULTS: Neuroticism was consistently associated with higher frailty, especially on the subjective index. In contrast, openness and extraversion were linked to lower objective frailty. Perceived stress emerged as the strongest mediator of the neuroticism-frailty link, followed by waist-to-hip ratio (WHR), smoking and resilience. For openness, resilience and WHR contributed modestly to its protective effect; extraversion's benefit was primarily mediated by social support. Distinct mediation patterns emerged across personality traits and frailty types, underscoring the complexity of these relationships. CONCLUSION: Personality traits, particularly neuroticism, openness, and extraversion, are meaningfully related to frailty via psychological and behavioral mechanisms. Findings support the integration of psychosocial resources into frailty prevention and healthy aging strategies.
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