Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examined whether accelerated biological aging is associated with cognitive impairment, whether lifestyle modifies this association, and how genetic background influences these relationships in Chinese older adults. In this cross-sectional study (2022-2023), 7,033 participants from southwestern China were included. Accelerated biological aging was calculated as the residual difference between biological age (based on 10 biomarkers) and chronological age. Lifestyle was assessed via a composite index (smoking, alcohol, physical activity, diet, sleep). Cognitive function was measured using the Chinese Mini-Mental State Examination (C-MMSE), and genetic risk was evaluated through polygenic scores and APOE ε4 status. Linear and logistic regression models assessed associations between accelerated aging and cognition. Accelerated biological aging was associated with lower MMSE scores (β = -0.243, 95% CI: -0.354, -0.133) and higher cognitive impairment prevalence (OR = 1.098, 95% CI: 1.040, 1.158). An unhealthy lifestyle exacerbated cognitive impairment in biologically older individuals (RERI = 0.25). Those with both accelerated aging and unhealthy lifestyle had the lowest MMSE scores (β = -1.424, 95% CI: -1.846, -1.003) and highest odds of cognitive impairment (OR = 1.467, 95% CI: 1.194, 1.803). These effects were consistent across all genetic background subgroups. Accelerated aging was associated with lower cognitive function, especially in individuals with unhealthy lifestyles, regardless of genetic susceptibility. This highlights lifestyle modification as a potential intervention target for aging-related cognitive impairment.
{"title":"Interplay of Accelerated Biological Aging, Lifestyle Factors, and Genetic Susceptibility in Cognitive Function: A Community Study.","authors":"Tianpei Ma,Xin Chen,Qingwen Zhao,Xinyin Xu,Xingyu Zhang,Xiaoxue Liu,Diji Zhuoma,Mengjie Hu,Haiyu Yan,Lei Lin,Ke Jiang,Xinyang Dui,Xunying Zhao,Xueyao Wu,Jinyu Xiao,Xia Jiang,Tao Zhang,Mengyu Fan,Lu Long,Ying Deng,Jiaqiang Liao,Jiayuan Li","doi":"10.1093/gerona/glaf277","DOIUrl":"https://doi.org/10.1093/gerona/glaf277","url":null,"abstract":"Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examined whether accelerated biological aging is associated with cognitive impairment, whether lifestyle modifies this association, and how genetic background influences these relationships in Chinese older adults. In this cross-sectional study (2022-2023), 7,033 participants from southwestern China were included. Accelerated biological aging was calculated as the residual difference between biological age (based on 10 biomarkers) and chronological age. Lifestyle was assessed via a composite index (smoking, alcohol, physical activity, diet, sleep). Cognitive function was measured using the Chinese Mini-Mental State Examination (C-MMSE), and genetic risk was evaluated through polygenic scores and APOE ε4 status. Linear and logistic regression models assessed associations between accelerated aging and cognition. Accelerated biological aging was associated with lower MMSE scores (β = -0.243, 95% CI: -0.354, -0.133) and higher cognitive impairment prevalence (OR = 1.098, 95% CI: 1.040, 1.158). An unhealthy lifestyle exacerbated cognitive impairment in biologically older individuals (RERI = 0.25). Those with both accelerated aging and unhealthy lifestyle had the lowest MMSE scores (β = -1.424, 95% CI: -1.846, -1.003) and highest odds of cognitive impairment (OR = 1.467, 95% CI: 1.194, 1.803). These effects were consistent across all genetic background subgroups. Accelerated aging was associated with lower cognitive function, especially in individuals with unhealthy lifestyles, regardless of genetic susceptibility. This highlights lifestyle modification as a potential intervention target for aging-related cognitive impairment.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jatupol Kositsawat,George A Kuchel,Kelin Zhong,Shangshu Zhao,Richard H Fortinsky,Chia-Ling Kuo
BACKGROUNDAging is multifactorial, yet aging research emphasizes independent risk factors. Endocrine and inflammatory factors have been linked to opposing and synergistic associations with suboptimal aging.METHODSGiven 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. BAA (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.RESULTSWe 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 to 0.583) years at CRP z-score 2 compared to 0.121 (95% CI 0.120 to 0.122) years at CRP z-score 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. 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.CONCLUSIONSOur 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.
衰老是一个多因素的过程，但衰老研究强调的是独立的危险因素。内分泌和炎症因素与亚理想衰老有拮抗和协同作用。方法考虑到多因素非线性方法的重要性，我们在313444名英国生物银行参与者中研究了维生素D缺乏症(VDD; 25(OH)D) < 20 ng/mL)和高c反应蛋白（CRP）水平（≥2.6 mg/L；在所包括样本中的第三个四分位数）与生物衰老加速（BAA）的相互作用。BAA（实际年龄<预期年龄）来源于PhenoAgeAccel（根据实际年龄和协变量调整的表型年龄（PhenoAge））。25(OH)D和CRP水平与BAA使用限制三次样条回归模型相关联。结果我们观察到CRP对VDD-BAA关联的调节作用，以及25(OH)D对高CRP- baa关联的调节作用。VDD患者的PhenoAgeAccel值在CRP z-score 2时为0.576 （95% CI 0.570至0.583）年，而在CRP z-score 0时为0.121 （95% CI 0.120至0.122）年。与25(OH)D和BAA呈u型关系相反，所有较高的CRP水平都与较高的BAA密切相关。在CRP水平较高的参与者中，VDD和BAA之间的关联更大，然而，无论维生素D水平如何，高CRP水平的参与者表现出相似的BAA。结论我们的研究结果说明了这些风险因素的非线性和相互作用性质，强调了通过精确老年学开发更有针对性的干预措施来针对衰老轨迹的异质性的重要性。方法可能包括针对VDD和炎症个体的炎症干预。
{"title":"The nonlinear U-shaped association between vitamin D deficiency and biological aging acceleration is enhanced in individuals with higher inflammation levels.","authors":"Jatupol Kositsawat,George A Kuchel,Kelin Zhong,Shangshu Zhao,Richard H Fortinsky,Chia-Ling Kuo","doi":"10.1093/gerona/glaf272","DOIUrl":"https://doi.org/10.1093/gerona/glaf272","url":null,"abstract":"BACKGROUNDAging is multifactorial, yet aging research emphasizes independent risk factors. Endocrine and inflammatory factors have been linked to opposing and synergistic associations with suboptimal aging.METHODSGiven 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. BAA (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.RESULTSWe 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 to 0.583) years at CRP z-score 2 compared to 0.121 (95% CI 0.120 to 0.122) years at CRP z-score 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. 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.CONCLUSIONSOur 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.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laboratory inbred strains respond strongly to dietary restriction (DR), whereas genetically diverse populations may not experience comparable benefits. The exceptionally short-lived fish, Nothobranchius furzeri, offers several genetically distinct captive populations; however, only the severely inbred GRZ strain has been tested for DR effects. Here, individually kept males (N = 111) of the outbred MZCS 222 strain of N. furzeri were assigned to 1/high-protein diet and two DR forms: 2/low-protein (isocaloric to high-protein but half the protein concentration), or 3/caloric-restriction (half the dose of HP at the feeding time). Neither form of DR significantly extended the lifespan of N. furzeri males. The limited efficacy of protein and caloric restriction in outbred N. furzeri may stem from insensitivity to these forms of DR or from the genetic diversity of the strain in comparison to earlier reported life extension through intermittent fasting in the inbred GRZ strain.
实验室自交系对饮食限制（DR）反应强烈，而遗传多样性种群可能没有类似的益处。这种特别短命的鱼，狐尾Nothobranchius furzeri，提供了几个基因上不同的圈养种群；然而，只有严重自交系的GRZ菌株进行了DR效应测试。在这里，单独饲养的MZCS 222型furzeri N = 111只雄虫（N = 111）被分配到1/高蛋白饮食和两种DR形式：2/低蛋白（等量热量到高蛋白，但蛋白质浓度减半），或3/热量限制（饲喂时HP剂量的一半）。两种形式的DR均不能显著延长狐尾扁虱雄性的寿命。在近交系中限制蛋白质和热量的有限效果可能源于对这些DR形式的不敏感，或者与早期报道的近交系GRZ菌株通过间歇性禁食延长寿命相比，该菌株的遗传多样性。
{"title":"Neither caloric nor protein restriction increases the male lifespan of outbred short-lived fish.","authors":"Jakub Žák,Martin Reichard","doi":"10.1093/gerona/glaf278","DOIUrl":"https://doi.org/10.1093/gerona/glaf278","url":null,"abstract":"Laboratory inbred strains respond strongly to dietary restriction (DR), whereas genetically diverse populations may not experience comparable benefits. The exceptionally short-lived fish, Nothobranchius furzeri, offers several genetically distinct captive populations; however, only the severely inbred GRZ strain has been tested for DR effects. Here, individually kept males (N = 111) of the outbred MZCS 222 strain of N. furzeri were assigned to 1/high-protein diet and two DR forms: 2/low-protein (isocaloric to high-protein but half the protein concentration), or 3/caloric-restriction (half the dose of HP at the feeding time). Neither form of DR significantly extended the lifespan of N. furzeri males. The limited efficacy of protein and caloric restriction in outbred N. furzeri may stem from insensitivity to these forms of DR or from the genetic diversity of the strain in comparison to earlier reported life extension through intermittent fasting in the inbred GRZ strain.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johanna Pöyhönen, Hanna-Maria Roitto, Jenni Lehtisalo, Esko Levälahti, Timo Strandberg, Miia Kivipelto, Jenni Kulmala, Riitta Antikainen, Hilkka Soininen, Jaakko Tuomilehto, Tiina Laatikainen, Tiia Ngandu
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 modified Fried phenotype and MCI by lowest quintile in Neuropsychological Test Battery z score. Having pre-frailty/frailty and MCI was classified as CF. Transition probabilities and predictiveness of CF by four 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 two years was higher in the control group (RR 1.88, p = 0.003). The intervention effect was not modified by baseline CF (p = 0.493). Reversal from CF to no-CF group was more likely in the intervention group, and progression to or persisting with CF in the control group. Compared with healthy participants (n = 401) at baseline, MCI group (n = 244) had RR of 5.10, pre-frail/frail (n = 336) of 3.06, and CF of 30.61 for having CF at two years, with no difference between MCI and pre-frail/frail groups (p = 0.116). Conclusions The two-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.
{"title":"Impact of Multidomain Lifestyle Intervention on Dynamics of Cognitive Frailty: Post-hoc Analysis of the FINGER Trial","authors":"Johanna Pöyhönen, Hanna-Maria Roitto, Jenni Lehtisalo, Esko Levälahti, Timo Strandberg, Miia Kivipelto, Jenni Kulmala, Riitta Antikainen, Hilkka Soininen, Jaakko Tuomilehto, Tiina Laatikainen, Tiia Ngandu","doi":"10.1093/gerona/glaf275","DOIUrl":"https://doi.org/10.1093/gerona/glaf275","url":null,"abstract":"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 modified Fried phenotype and MCI by lowest quintile in Neuropsychological Test Battery z score. Having pre-frailty/frailty and MCI was classified as CF. Transition probabilities and predictiveness of CF by four 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 two years was higher in the control group (RR 1.88, p = 0.003). The intervention effect was not modified by baseline CF (p = 0.493). Reversal from CF to no-CF group was more likely in the intervention group, and progression to or persisting with CF in the control group. Compared with healthy participants (n = 401) at baseline, MCI group (n = 244) had RR of 5.10, pre-frail/frail (n = 336) of 3.06, and CF of 30.61 for having CF at two years, with no difference between MCI and pre-frail/frail groups (p = 0.116). Conclusions The two-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.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuel E Hernandez, Robert W Motl, Frederick W Foley, Meltem Izzetoglu, Mark Wagshul, Roee Holtzer
Background Falls and gait variability are prevalent in older adults with and without multiple sclerosis. Gait variability has been associated with an increased likelihood of reporting falls in older adults, yet its prediction of falls in older adults with multiple sclerosis remains unclear. Methods We examined whether gait variability measured under single- and dual-task walking conditions predicted falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) and healthy older adults (HOA). HOA (n = 106, mean age=69 years) and OAMS (n = 95, mean age=65 years) completed a single and dual-task walking paradigm and reported falls during a longitudinal follow-up. Gait variability was measured using an instrumented walkway. Results Cox-regression models indicated that larger coefficients of variation (CVs) of dual-task-walk stride length (HR = 1.04, p = 0.017), dual-task-walk swing time (HR = 1.03, p = 0.044), and single-task-walk swing time (HR = 1.05, p < 0.001) were significantly associated with increased hazards of incident falls, even after adjustment. Cohort-stratified cox-regression models with adjustment showed that larger single-task-walk swing time CV was associated with a higher hazard of incident falls in HOA (HR = 1.10, p = 0.028), while larger CVs in dual-task-walk stride velocity (HR = 1.04, p = 0.017), stride length (HR = 1.06, p = 0.016), and swing time (HR = 1.05, p = 0.018) were significantly associated with a higher hazard of incident falls in OAMS. Conclusions Findings suggest that greater gait variability predicts increased fall risk in OAMS and HOA participants, with a 1% increase in CV associated with a 4-10% fall hazard increase. However, walking condition influenced this association with single-task-walk variability being predictive in HOA, while dual-task-walk variability is more predictive in OAMS.
背景：跌倒和步态变异性在有或没有多发性硬化症的老年人中很普遍。步态变异性与老年人报告跌倒的可能性增加有关，但其对多发性硬化症老年人跌倒的预测仍不清楚。方法：我们研究了在单任务和双任务步行条件下测量的步态变异性是否能预测多发性硬化症（OAMS）和健康老年人（HOA）的纵向随访。HOA （n = 106，平均年龄=69岁）和OAMS （n = 95，平均年龄=65岁）完成了单任务和双任务步行范式，并在纵向随访中报告跌倒。步态变异性测量使用仪器人行道。结果cox回归模型显示，即使经过调整，双任务步行步幅（HR = 1.04, p = 0.017）、双任务步行摆动时间（HR = 1.03, p = 0.044）和单任务步行摆动时间（HR = 1.05, p < 0.001）的较大变异系数（cv）也与意外跌倒风险增加显著相关。校正后的队列分层cox回归模型显示，较大的单任务步行摆动时间CV与较高的HOA事件跌倒风险相关（HR = 1.10, p = 0.028），而较大的双任务步行步幅CV （HR = 1.04, p = 0.017）、步幅长度CV （HR = 1.06, p = 0.016）和摆动时间CV （HR = 1.05, p = 0.018）与较高的OAMS事件跌倒风险相关。研究结果表明，更大的步态变异性预示着OAMS和HOA参与者跌倒风险增加，CV增加1%与跌倒风险增加4-10%相关。然而，步行条件影响了这种关联，单任务步行变异性在HOA中具有预测性，而双任务步行变异性在OAMS中更具预测性。
{"title":"Gait variability predicts falls in older adults with multiple sclerosis","authors":"Manuel E Hernandez, Robert W Motl, Frederick W Foley, Meltem Izzetoglu, Mark Wagshul, Roee Holtzer","doi":"10.1093/gerona/glaf269","DOIUrl":"https://doi.org/10.1093/gerona/glaf269","url":null,"abstract":"Background Falls and gait variability are prevalent in older adults with and without multiple sclerosis. Gait variability has been associated with an increased likelihood of reporting falls in older adults, yet its prediction of falls in older adults with multiple sclerosis remains unclear. Methods We examined whether gait variability measured under single- and dual-task walking conditions predicted falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) and healthy older adults (HOA). HOA (n = 106, mean age=69 years) and OAMS (n = 95, mean age=65 years) completed a single and dual-task walking paradigm and reported falls during a longitudinal follow-up. Gait variability was measured using an instrumented walkway. Results Cox-regression models indicated that larger coefficients of variation (CVs) of dual-task-walk stride length (HR = 1.04, p = 0.017), dual-task-walk swing time (HR = 1.03, p = 0.044), and single-task-walk swing time (HR = 1.05, p &lt; 0.001) were significantly associated with increased hazards of incident falls, even after adjustment. Cohort-stratified cox-regression models with adjustment showed that larger single-task-walk swing time CV was associated with a higher hazard of incident falls in HOA (HR = 1.10, p = 0.028), while larger CVs in dual-task-walk stride velocity (HR = 1.04, p = 0.017), stride length (HR = 1.06, p = 0.016), and swing time (HR = 1.05, p = 0.018) were significantly associated with a higher hazard of incident falls in OAMS. Conclusions Findings suggest that greater gait variability predicts increased fall risk in OAMS and HOA participants, with a 1% increase in CV associated with a 4-10% fall hazard increase. However, walking condition influenced this association with single-task-walk variability being predictive in HOA, while dual-task-walk variability is more predictive in OAMS.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"226 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aitana Vázquez-Fernández,Humberto Yévenes-Briones,Ana Baylin,Francisco F Caballero,Esther Lopez-Garcia
BACKGROUNDMultimorbidity is a major determinant of lifespan in older adults. We aimed to examine the association between overall, healthy and unhealthy Low-Carbohydrate diets (LCD) and Low-Fat diets (LFD) with the incidence of multimorbidity.METHODS112,710 individuals (40-70 years) from the UK Biobank were included. Food consumption was assessed using up to five 24-hour dietary recalls. LCD and LFD scores were calculated based on macronutrient quality. We calculated three versions of each score-overall, healthy and unhealthy. Multimorbidity was defined as the coexistence of ≥ 2 of nine chronic diseases, including cancer, chronic obstructive pulmonary disease, dementia, Parkinson's disease, stroke, depression, osteoarthritis, diabetes, and coronary heart disease.RESULTSThere were 8,387 individuals with multimorbidity during a median follow-up of 10.7-years. Overall LCD and LFD scores were not associated with higher multimorbidity risk. There was a higher multimorbidity risk for individuals in the highest quintile (Q5) of unhealthy LCD vs. lowest quintile (Q1) [fully adjusted hazard ratio (HR): 1.07, 95%CI: 1.01, 1.15, p-trend=.16] overall as well as among non-tobacco smokers [1.11 (1.00, 1.23, p-trend=.09]. The unhealthy LFD score was associated with multimorbidity overall [1.07 (1.00, 1.14), p-trend=.07] and never-smokers [1.12 (1.01, 1.24); p-trend=.01]. Healthy scores results were less consistent. The plant protein component had an inverse association with incident multimorbidity risk, whereas the low-quality-fat and animal protein components were each associated with higher risk of multimorbidity.CONCLUSIONDiet scores defined only by the total amount of carbohydrates or fat were not associated with risk of multimorbidity. Unhealthy diet scores including low-quality macronutrients and animal protein were associated with increased risk of multimorbidity.
{"title":"Macronutrient content and quality, and risk of multimorbidity in the UK biobank.","authors":"Aitana Vázquez-Fernández,Humberto Yévenes-Briones,Ana Baylin,Francisco F Caballero,Esther Lopez-Garcia","doi":"10.1093/gerona/glaf267","DOIUrl":"https://doi.org/10.1093/gerona/glaf267","url":null,"abstract":"BACKGROUNDMultimorbidity is a major determinant of lifespan in older adults. We aimed to examine the association between overall, healthy and unhealthy Low-Carbohydrate diets (LCD) and Low-Fat diets (LFD) with the incidence of multimorbidity.METHODS112,710 individuals (40-70 years) from the UK Biobank were included. Food consumption was assessed using up to five 24-hour dietary recalls. LCD and LFD scores were calculated based on macronutrient quality. We calculated three versions of each score-overall, healthy and unhealthy. Multimorbidity was defined as the coexistence of ≥ 2 of nine chronic diseases, including cancer, chronic obstructive pulmonary disease, dementia, Parkinson's disease, stroke, depression, osteoarthritis, diabetes, and coronary heart disease.RESULTSThere were 8,387 individuals with multimorbidity during a median follow-up of 10.7-years. Overall LCD and LFD scores were not associated with higher multimorbidity risk. There was a higher multimorbidity risk for individuals in the highest quintile (Q5) of unhealthy LCD vs. lowest quintile (Q1) [fully adjusted hazard ratio (HR): 1.07, 95%CI: 1.01, 1.15, p-trend=.16] overall as well as among non-tobacco smokers [1.11 (1.00, 1.23, p-trend=.09]. The unhealthy LFD score was associated with multimorbidity overall [1.07 (1.00, 1.14), p-trend=.07] and never-smokers [1.12 (1.01, 1.24); p-trend=.01]. Healthy scores results were less consistent. The plant protein component had an inverse association with incident multimorbidity risk, whereas the low-quality-fat and animal protein components were each associated with higher risk of multimorbidity.CONCLUSIONDiet scores defined only by the total amount of carbohydrates or fat were not associated with risk of multimorbidity. Unhealthy diet scores including low-quality macronutrients and animal protein were associated with increased risk of multimorbidity.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Accurate diagnosis and assessment of mild cognitive impairment (MCI) are essential. The efficacy of saccades in the detection of MCI lacks validation through large-scale clinical trials. Methods All eligible participants underwent saccadic assessment in four tasks and cognitive assessment. MCI diagnoses were made on the basis of clinical indicators and MRI by experienced physicians. The physicians were blinded to the saccade experiments and the operators of saccade experiments were blind to the diagnosis of physicians. The classification models based on machine learning was constructed for assessing the diagnostic accuracy of MCI based on saccadic parameters. Results Of the 559 residents who consented to participate, 383 (153 with MCI and 230 controls) were completely assessed. The classification model trained by saccadic parameters achieved high accuracy in dissociating MCI and control with AUROC of 0.945 (95% CI, 0.924-0.964), sensitivity of 0.824 (95% CI, 0.769-0.886) and specificity of 0.904 (95% CI, 0.867-0.935). The parameters of the memory-guided and antisaccade tasks demonstrated better diagnostic efficacy. The saccade model also exhibited a good diagnostic value in patients with borderline cognition being defined by the score of MoCA. When the borderline cognition was defined as 23-27 of MoCA score, the diagnosing accuracy of MCI based on saccadic parameters resulted with AUROC of 0.911 (95% CI: 0.836-0.972), sensitivity of 0.929 (95% CI, 0.762-1.000) and specificity of 0.796 (95% CI, 0.718-0.863). Conclusions Saccades can distinguish MCI from controls with great accuracy, offering a sensitive and objective diagnostic aid of MCI, especially in participants with borderline cognition.
{"title":"Diagnostic value of saccades in mild cognitive impairment (MCI): a community-based study","authors":"Leihao Sha, Hua Li, Anjiao Peng, Huajun Yang, Xin Liu, Hongjian Zhao, Wenbo Ma, Qiulei Hong, Yusha Tang, Mingsha Zhang, Lei Chen","doi":"10.1093/gerona/glaf264","DOIUrl":"https://doi.org/10.1093/gerona/glaf264","url":null,"abstract":"Background Accurate diagnosis and assessment of mild cognitive impairment (MCI) are essential. The efficacy of saccades in the detection of MCI lacks validation through large-scale clinical trials. Methods All eligible participants underwent saccadic assessment in four tasks and cognitive assessment. MCI diagnoses were made on the basis of clinical indicators and MRI by experienced physicians. The physicians were blinded to the saccade experiments and the operators of saccade experiments were blind to the diagnosis of physicians. The classification models based on machine learning was constructed for assessing the diagnostic accuracy of MCI based on saccadic parameters. Results Of the 559 residents who consented to participate, 383 (153 with MCI and 230 controls) were completely assessed. The classification model trained by saccadic parameters achieved high accuracy in dissociating MCI and control with AUROC of 0.945 (95% CI, 0.924-0.964), sensitivity of 0.824 (95% CI, 0.769-0.886) and specificity of 0.904 (95% CI, 0.867-0.935). The parameters of the memory-guided and antisaccade tasks demonstrated better diagnostic efficacy. The saccade model also exhibited a good diagnostic value in patients with borderline cognition being defined by the score of MoCA. When the borderline cognition was defined as 23-27 of MoCA score, the diagnosing accuracy of MCI based on saccadic parameters resulted with AUROC of 0.911 (95% CI: 0.836-0.972), sensitivity of 0.929 (95% CI, 0.762-1.000) and specificity of 0.796 (95% CI, 0.718-0.863). Conclusions Saccades can distinguish MCI from controls with great accuracy, offering a sensitive and objective diagnostic aid of MCI, especially in participants with borderline cognition.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes C Michaelian,Kira Trares,Joshua Stevenson-Hoare,Bernd Holleczek,Ben Schöttker,Hermann Brenner
BACKGROUNDWhile previous research has demonstrated that frailty is associated with increased dementia risk over time, large multi-decade prospective population-based cohort studies remain limited. Furthermore, the association between lower grip strength and blood-based biomarkers of neuropathology and global cognitive function remains under-investigated.METHODSWe investigated the relationship between varying levels of baseline frailty (measured using a deficit accumulation Frailty Index) and dementia incidence over 17 years, as well as associations of grip strength (hand, pinch and key, assessed at 8- and 14-year follow-up) with blood-based biomarkers of neuropathology (year 8) and with global cognitive function (year 14) in a population-representative cohort of 9,940 mid-to-late life (50-75 years) individuals.RESULTSIn a subsample of 6,357 participants with available dementia information at 17-year follow-up (mean age at baseline [SD], 61.7 [6.6] years; female, 54.3%), 516 received an all-cause dementia diagnosis. Over this time, individuals in the highest frailty index quintile demonstrated a significantly higher risk of all-cause dementia (HR, 1.75; 95% CI, 1.18-2.60) and a vascular dementia diagnosis (HR, 2.44; 95% CI, 1.22-4.91). Cross-sectionally, lower handgrip strength was associated with elevated blood levels of NfL (β=-0.01, p=0.007) and pTau181 (β=-0.004, p=0.017) at 8-year follow-up, as well as poorer cognitive function on the Montreal Cognitive Assessment (MoCA) (β = 0.02, p=0.037) at 14-year follow-up.CONCLUSIONSThis study strengthens evidence that frailty is a risk factor for dementia in mid-to-late life. It also suggests that it is of considerable importance to assess frailty and grip strength in individuals 'at risk' of cognitive decline.
{"title":"TITLE: Frailty, grip strength, blood-based biomarkers of neuropathology and incident dementia: a 17-year longitudinal population study.","authors":"Johannes C Michaelian,Kira Trares,Joshua Stevenson-Hoare,Bernd Holleczek,Ben Schöttker,Hermann Brenner","doi":"10.1093/gerona/glaf268","DOIUrl":"https://doi.org/10.1093/gerona/glaf268","url":null,"abstract":"BACKGROUNDWhile previous research has demonstrated that frailty is associated with increased dementia risk over time, large multi-decade prospective population-based cohort studies remain limited. Furthermore, the association between lower grip strength and blood-based biomarkers of neuropathology and global cognitive function remains under-investigated.METHODSWe investigated the relationship between varying levels of baseline frailty (measured using a deficit accumulation Frailty Index) and dementia incidence over 17 years, as well as associations of grip strength (hand, pinch and key, assessed at 8- and 14-year follow-up) with blood-based biomarkers of neuropathology (year 8) and with global cognitive function (year 14) in a population-representative cohort of 9,940 mid-to-late life (50-75 years) individuals.RESULTSIn a subsample of 6,357 participants with available dementia information at 17-year follow-up (mean age at baseline [SD], 61.7 [6.6] years; female, 54.3%), 516 received an all-cause dementia diagnosis. Over this time, individuals in the highest frailty index quintile demonstrated a significantly higher risk of all-cause dementia (HR, 1.75; 95% CI, 1.18-2.60) and a vascular dementia diagnosis (HR, 2.44; 95% CI, 1.22-4.91). Cross-sectionally, lower handgrip strength was associated with elevated blood levels of NfL (β=-0.01, p=0.007) and pTau181 (β=-0.004, p=0.017) at 8-year follow-up, as well as poorer cognitive function on the Montreal Cognitive Assessment (MoCA) (β = 0.02, p=0.037) at 14-year follow-up.CONCLUSIONSThis study strengthens evidence that frailty is a risk factor for dementia in mid-to-late life. It also suggests that it is of considerable importance to assess frailty and grip strength in individuals 'at risk' of cognitive decline.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"138 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDThe aim of this study was to explore the developmental trajectories of social participation and cognitive function, as well as their interaction.METHODSThe study enrolled 6,242 participants from the China Health and Retirement Longitudinal Study, with a mean age (SD) of 58.81 (7.94) years and 45.3% being female. Linear mixed models (LMM) were used in the research to examine the association between social participation and cognitive function. Then, we performed latent growth curve models (LGCM) and cross-lagged panel models (CLPM) to explore the 5-year bidirectional causal relationship from 2015 to 2020.RESULTSDuring the five-year follow-up (2015, 2018, & 2020), baseline social participation was related to subsequent cognitive function (β = 0.190, 95% CI: 0.138-0.244, P < 0.001), mental intactness (β = 0.092, 95% CI: 0.056-0.128, P < 0.001) and episodic memory (β = 0.099, 95% CI: 0.068-0.129, P < 0.001). Baseline cognitive function (β = 0.033, 95% CI: 0.021-0.045, P < 0.001), mental intactness (β = 0.035, 95% CI: 0.017-0.052, P < 0.001) and episodic memory (β = 0.050, 95% CI: 0.029-0.070, P < 0.001) were significantly related to subsequent social participation. LGCM showed that the level of social participation increases, while cognitive function remains stable, with the initial levels of both factors mutually influencing each other. The rate of change in social participation significantly predicts the rate of change in cognitive function, and vice versa. CLPM results further support the bidirectional causal relationship.CONCLUSIONOur study reveals the intricate dynamic association between social participation and cognitive function. The findings support the positive effects of social participation on healthy cognitive aging, while robust cognitive function enhances social participation in late midlife and older adulthood.
本研究旨在探讨社会参与与认知功能的发展轨迹及其相互作用。方法从中国健康与退休纵向研究中招募6242名参与者，平均年龄（SD）为58.81（7.94）岁，其中45.3%为女性。采用线性混合模型（LMM）研究社会参与与认知功能之间的关系。利用潜在增长曲线模型（LGCM）和交叉滞后面板模型（CLPM）分析了2015 - 2020年的5年双向因果关系。结果在5年随访期间（2015年、2018年和2020年），基线社会参与与随后的认知功能（β = 0.190, 95% CI: 0.138-0.244, P < 0.001）、精神完整性（β = 0.092, 95% CI: 0.056-0.128, P < 0.001）和情景记忆（β = 0.099, 95% CI: 0.068-0.129, P < 0.001）相关。基线认知功能（β = 0.033, 95% CI: 0.021-0.045, P < 0.001）、精神完整性（β = 0.035, 95% CI: 0.017-0.052, P < 0.001）和情景记忆（β = 0.050, 95% CI: 0.029-0.070, P < 0.001）与随后的社会参与显著相关。LGCM表明，社会参与水平提高，认知功能保持稳定，两者的初始水平相互影响。社会参与的变化率显著地预测了认知功能的变化率，反之亦然。CLPM结果进一步支持双向因果关系。结论本研究揭示了社会参与与认知功能之间复杂的动态关联。研究结果支持社会参与对健康认知衰老的积极影响，而强健的认知功能可以促进中年晚期和老年的社会参与。
{"title":"The Dynamic Trends and Causal Effects of Social Participation and Cognitive Function Among Middle-Aged and Older Adults: A Longitudinal Study in China.","authors":"Lin Sun,Jingru Wang,Yuting Kang,Pengjun Zhang","doi":"10.1093/gerona/glaf266","DOIUrl":"https://doi.org/10.1093/gerona/glaf266","url":null,"abstract":"BACKGROUNDThe aim of this study was to explore the developmental trajectories of social participation and cognitive function, as well as their interaction.METHODSThe study enrolled 6,242 participants from the China Health and Retirement Longitudinal Study, with a mean age (SD) of 58.81 (7.94) years and 45.3% being female. Linear mixed models (LMM) were used in the research to examine the association between social participation and cognitive function. Then, we performed latent growth curve models (LGCM) and cross-lagged panel models (CLPM) to explore the 5-year bidirectional causal relationship from 2015 to 2020.RESULTSDuring the five-year follow-up (2015, 2018, & 2020), baseline social participation was related to subsequent cognitive function (β = 0.190, 95% CI: 0.138-0.244, P < 0.001), mental intactness (β = 0.092, 95% CI: 0.056-0.128, P < 0.001) and episodic memory (β = 0.099, 95% CI: 0.068-0.129, P < 0.001). Baseline cognitive function (β = 0.033, 95% CI: 0.021-0.045, P < 0.001), mental intactness (β = 0.035, 95% CI: 0.017-0.052, P < 0.001) and episodic memory (β = 0.050, 95% CI: 0.029-0.070, P < 0.001) were significantly related to subsequent social participation. LGCM showed that the level of social participation increases, while cognitive function remains stable, with the initial levels of both factors mutually influencing each other. The rate of change in social participation significantly predicts the rate of change in cognitive function, and vice versa. CLPM results further support the bidirectional causal relationship.CONCLUSIONOur study reveals the intricate dynamic association between social participation and cognitive function. The findings support the positive effects of social participation on healthy cognitive aging, while robust cognitive function enhances social participation in late midlife and older adulthood.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federico Bellelli, Maria Cristina Ferrara, Alice Margherita Ornago, Elena Pinardi, Alberto Finazzi, Ernesto Consorti, Davide Angioni, Chukwuma Okoye, Giuseppe Bellelli
Background Benzodiazepines (BZDs) are commonly used in older populations despite their association with multiple adverse outcomes. However, the impact of continuing versus deprescribing BZDs during hospitalization on short-term mortality after discharge remains uncertain. This study aims to evaluate the association of BZD-use at hospital discharge with 6-month mortality and explore whether in-hospital deprescribing modifies mortality risk. Methods This is a retrospective analysis of prospectively collected data from patients (aged 66–101 years) consecutively admitted to an Acute Geriatric Unit (AGU). Upon admission, all patients underwent a Comprehensive Geriatric Assessment (CGA), including functional status, comorbidities, and medications review. A multivariable Cox-regression model was used to evaluate the relationship between 6-month mortality and BZD prescription at hospital discharge (BZD non-users, BZD at discharge, and BZD deprescribed). Results Overall, 1375 patients (median age: 85.5 [IQR: 48-77, 55% females]) were included. Following therapeutic reconciliation, the BZD at discharge group was younger (p = 0.029), had lower frailty (p = 0.031), cognitive decline (p = 0.043) and in-hospital delirium (p < 0.001) prevalence than the BZD non-users and BZD deprescribed groups. The BZD at discharge group (n = 130) showed a higher risk of all-cause 6-month mortality compared to BZD non-users (n = 1066) (HR: 1.64; 95%CI: 1.14-2.37). Conversely, patients in whom BZDs were deprescribed during hospitalization (n = 179) exhibited a similar mortality risk as non-users (HR: 0.97; 95%CI: 0.68–1.39). Conclusions BZDs prescription on hospital discharge was associated with an increased risk of 6-month mortality, whereas deprescription may mitigate this excess risk. Our data suggest that hospitalization may represent an opportunity to safely deprescribe BZDs in a controlled setting.
{"title":"Benzodiazepine Exposure and 6-Month Mortality in Older Adults Post-Hospitalization: Time to Consider Deprescribing?","authors":"Federico Bellelli, Maria Cristina Ferrara, Alice Margherita Ornago, Elena Pinardi, Alberto Finazzi, Ernesto Consorti, Davide Angioni, Chukwuma Okoye, Giuseppe Bellelli","doi":"10.1093/gerona/glaf260","DOIUrl":"https://doi.org/10.1093/gerona/glaf260","url":null,"abstract":"Background Benzodiazepines (BZDs) are commonly used in older populations despite their association with multiple adverse outcomes. However, the impact of continuing versus deprescribing BZDs during hospitalization on short-term mortality after discharge remains uncertain. This study aims to evaluate the association of BZD-use at hospital discharge with 6-month mortality and explore whether in-hospital deprescribing modifies mortality risk. Methods This is a retrospective analysis of prospectively collected data from patients (aged 66–101 years) consecutively admitted to an Acute Geriatric Unit (AGU). Upon admission, all patients underwent a Comprehensive Geriatric Assessment (CGA), including functional status, comorbidities, and medications review. A multivariable Cox-regression model was used to evaluate the relationship between 6-month mortality and BZD prescription at hospital discharge (BZD non-users, BZD at discharge, and BZD deprescribed). Results Overall, 1375 patients (median age: 85.5 [IQR: 48-77, 55% females]) were included. Following therapeutic reconciliation, the BZD at discharge group was younger (p = 0.029), had lower frailty (p = 0.031), cognitive decline (p = 0.043) and in-hospital delirium (p &lt; 0.001) prevalence than the BZD non-users and BZD deprescribed groups. The BZD at discharge group (n = 130) showed a higher risk of all-cause 6-month mortality compared to BZD non-users (n = 1066) (HR: 1.64; 95%CI: 1.14-2.37). Conversely, patients in whom BZDs were deprescribed during hospitalization (n = 179) exhibited a similar mortality risk as non-users (HR: 0.97; 95%CI: 0.68–1.39). Conclusions BZDs prescription on hospital discharge was associated with an increased risk of 6-month mortality, whereas deprescription may mitigate this excess risk. Our data suggest that hospitalization may represent an opportunity to safely deprescribe BZDs in a controlled setting.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"165 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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