Ryan S Falck, Ryan G Stein, Jennifer C Davis, Janice J Eng, Laura E Middleton, Peter A Hall, Teresa Liu-Ambrose
Background Exercise (EX) or cognitive and social enrichment (ENRICH) are two strategies for promoting cognition post-stroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown. Methods A three-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (i.e., ≥12 months since stroke). Participants were randomized to 2x/week EX, ENRICH, or balance and tone control (BAT). At baseline, device-measured sleep duration and efficiency were measured using wrist-worn actigraphy; self-reported quality was measured by Pittsburgh Sleep Quality Index (PSQI). Participants were categorized at baseline as having good or poor device-measured duration, device-measured efficiency, or self-reported quality based on PSQI. The primary cognitive outcome was Alzheimer’s Disease Assessment Scale Plus (ADAS-Cog-Plus) measured at baseline, 6 months (end of intervention), and 12 months (6-month follow-up). We examined if baseline sleep categorizations (i.e., good/poor) moderated effects of EX or ENRICH on ADAS-Cog-Plus. Results We enrolled 120 participants in the trial (EX=34; ENRICH=34; BAT=52). Sleep quality (i.e., device-measured sleep efficiency or self-reported sleep quality) categorization moderated effects of EX (but not ENRICH) on ADAS-Cog-Plus. Compared with BAT participants with poor sleep quality, EX participants with poor sleep quality had better ADAS-Cog-Plus performance at 6 months (estimated mean difference for those with poor device-measured sleep efficiency: -0.48; 95% CI:[-0.85, -0.10]; p=0.010); estimated mean difference for those with poor self-reported sleep quality: -0.38; 95% CI:[-0.70, -0.07]; p=0.014). There was no effect of EX on ADAS-Cog-Plus for participants with good sleep quality. Device-measured sleep duration did not moderate intervention effects. Conclusion Exercise is particularly beneficial in improving cognitive function in adults with chronic stroke and poor sleep quality.
{"title":"Does sleep moderate the effects of exercise training or complex mental and social activities on cognitive function in adults with chronic stroke? Secondary analysis of a randomized trial","authors":"Ryan S Falck, Ryan G Stein, Jennifer C Davis, Janice J Eng, Laura E Middleton, Peter A Hall, Teresa Liu-Ambrose","doi":"10.1093/gerona/glae264","DOIUrl":"https://doi.org/10.1093/gerona/glae264","url":null,"abstract":"Background Exercise (EX) or cognitive and social enrichment (ENRICH) are two strategies for promoting cognition post-stroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown. Methods A three-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (i.e., ≥12 months since stroke). Participants were randomized to 2x/week EX, ENRICH, or balance and tone control (BAT). At baseline, device-measured sleep duration and efficiency were measured using wrist-worn actigraphy; self-reported quality was measured by Pittsburgh Sleep Quality Index (PSQI). Participants were categorized at baseline as having good or poor device-measured duration, device-measured efficiency, or self-reported quality based on PSQI. The primary cognitive outcome was Alzheimer’s Disease Assessment Scale Plus (ADAS-Cog-Plus) measured at baseline, 6 months (end of intervention), and 12 months (6-month follow-up). We examined if baseline sleep categorizations (i.e., good/poor) moderated effects of EX or ENRICH on ADAS-Cog-Plus. Results We enrolled 120 participants in the trial (EX=34; ENRICH=34; BAT=52). Sleep quality (i.e., device-measured sleep efficiency or self-reported sleep quality) categorization moderated effects of EX (but not ENRICH) on ADAS-Cog-Plus. Compared with BAT participants with poor sleep quality, EX participants with poor sleep quality had better ADAS-Cog-Plus performance at 6 months (estimated mean difference for those with poor device-measured sleep efficiency: -0.48; 95% CI:[-0.85, -0.10]; p=0.010); estimated mean difference for those with poor self-reported sleep quality: -0.38; 95% CI:[-0.70, -0.07]; p=0.014). There was no effect of EX on ADAS-Cog-Plus for participants with good sleep quality. Device-measured sleep duration did not moderate intervention effects. Conclusion Exercise is particularly beneficial in improving cognitive function in adults with chronic stroke and poor sleep quality.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597139","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}
Patrick T Donahue, Aparna Balasubramanian, Qian-Li Xue, Jennifer A Schrack, Michelle C Carlson
Background Impaired respiratory function, measured via peak expiratory flow (PEF), has been associated with increased dementia risk. However, much of the current literature uses cross-sectional measures of PEF, whereas longitudinal relationships between changes in respiratory function and dementia risk are underexplored. Methods Using 10 years of data (2011-2021) from 2,439 adults ages 65 and older in the National Health and Aging Trends Study (NHATS), we examined whether 5-year changes in PEF (2011-2016) were associated with risk for incident dementia over the subsequent 5-year period (2017-2021). PEF slopes for each participant were estimated using linear mixed-effects models and then grouped into quartiles: rapid, moderate, mild, and no declines. Discrete-time Cox proportional hazards models were used to estimate the risk for incident dementia by PEF slope category, while controlling for several health and sociodemographic characteristics. Results After excluding dementia cases during the exposure window (2011-2016), we identified 338 cases of incident dementia (13.9%) between 2017-2021. Rapid PEF declines between 2011-2016 were associated with 85% higher risk for incident dementia between 2017-2021 compared to those with no declines in PEF (HR=1.85; 95% CI [1.24, 2.76]). Results were robust to several sensitivity analyses. Conclusions These findings demonstrate that declines in PEF may precede declines in cognition, suggesting that respiratory function may be an important dementia risk factor in older adults. Additionally, these findings highlight the utility of measuring PEF via a peak flow meter, which is a simple and inexpensive measure of respiratory function.
{"title":"Longitudinal Changes in Peak Expiratory Flow Predict Risk for Incident Dementia","authors":"Patrick T Donahue, Aparna Balasubramanian, Qian-Li Xue, Jennifer A Schrack, Michelle C Carlson","doi":"10.1093/gerona/glae249","DOIUrl":"https://doi.org/10.1093/gerona/glae249","url":null,"abstract":"Background Impaired respiratory function, measured via peak expiratory flow (PEF), has been associated with increased dementia risk. However, much of the current literature uses cross-sectional measures of PEF, whereas longitudinal relationships between changes in respiratory function and dementia risk are underexplored. Methods Using 10 years of data (2011-2021) from 2,439 adults ages 65 and older in the National Health and Aging Trends Study (NHATS), we examined whether 5-year changes in PEF (2011-2016) were associated with risk for incident dementia over the subsequent 5-year period (2017-2021). PEF slopes for each participant were estimated using linear mixed-effects models and then grouped into quartiles: rapid, moderate, mild, and no declines. Discrete-time Cox proportional hazards models were used to estimate the risk for incident dementia by PEF slope category, while controlling for several health and sociodemographic characteristics. Results After excluding dementia cases during the exposure window (2011-2016), we identified 338 cases of incident dementia (13.9%) between 2017-2021. Rapid PEF declines between 2011-2016 were associated with 85% higher risk for incident dementia between 2017-2021 compared to those with no declines in PEF (HR=1.85; 95% CI [1.24, 2.76]). Results were robust to several sensitivity analyses. Conclusions These findings demonstrate that declines in PEF may precede declines in cognition, suggesting that respiratory function may be an important dementia risk factor in older adults. Additionally, these findings highlight the utility of measuring PEF via a peak flow meter, which is a simple and inexpensive measure of respiratory function.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489752","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}
Fernando Gabriel Altamirano, Ivanna Castro-Pascual, Ivana Tamara Ponce, Cinthia Daiana Coria-Lucero, Ethelina Cargnelutti, Mariana Lucila Ferramola, Marcela Silvia Delgado, Ana Cecilia Anzulovich, María Gabriela Lacoste
Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.
{"title":"Late-onset caloric restriction improves cognitive performance and restores circadian patterns of neurotrophic, clock and epigenetic factors in the hippocampus of male old rats","authors":"Fernando Gabriel Altamirano, Ivanna Castro-Pascual, Ivana Tamara Ponce, Cinthia Daiana Coria-Lucero, Ethelina Cargnelutti, Mariana Lucila Ferramola, Marcela Silvia Delgado, Ana Cecilia Anzulovich, María Gabriela Lacoste","doi":"10.1093/gerona/glae252","DOIUrl":"https://doi.org/10.1093/gerona/glae252","url":null,"abstract":"Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489749","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}
Allyson K Palmer, Jennifer St. Sauver, Roger A Fielding, Elizabeth Atkinson, Thomas A White, Michaela McGree, Susan Weston, Nathan K LeBrasseur
Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index (BMI). After adjusting for age, sex, and race, we observed significant increases in activin A, Fas, MDC, PAI1, PARC, TNFR1, and VEGFA, and a significant decrease in RAGE, from normal weight, to overweight, to obesity BMI categories by linear regression in both cohorts (all p < 0.05). These results highlight the influence of BMI on circulating concentrations of senescence biomarkers.
{"title":"The influence of body mass index on biomarkers of cellular senescence in older adults","authors":"Allyson K Palmer, Jennifer St. Sauver, Roger A Fielding, Elizabeth Atkinson, Thomas A White, Michaela McGree, Susan Weston, Nathan K LeBrasseur","doi":"10.1093/gerona/glae251","DOIUrl":"https://doi.org/10.1093/gerona/glae251","url":null,"abstract":"Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index (BMI). After adjusting for age, sex, and race, we observed significant increases in activin A, Fas, MDC, PAI1, PARC, TNFR1, and VEGFA, and a significant decrease in RAGE, from normal weight, to overweight, to obesity BMI categories by linear regression in both cohorts (all p &lt; 0.05). These results highlight the influence of BMI on circulating concentrations of senescence biomarkers.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489746","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}
Robertina Giacconi, Francesco Piacenza, Fabrizio Maggi, Alexander Bürkle, María Moreno Villanueva, Lucia Mancinelli, Pietro Giorgio Spezia, Federica Novazzi, Francesca Drago Ferrante, Claudia Minosse, Paolo Antonio Grossi, Nicasio Mancini, Monia Cecati, Martijn E T Dollé, Eugène Jansen, Tilman Grune, Efstathios S Gonos, Claudio Franceschi, Miriam Capri, Birgit Weinberger, Ewa Sikora, Florence Debacq-Chainiaux, Wolfgang Stuetz, Mikko Hurme, P Eline Slagboom, Jürgen Bernhardt, Davide Gentilini, Luciano Calzari, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Fabrizia Lattanzio, Mauro Provinciali, Marco Malavolta
The implication of Torquetenovirus (TTV) in Ischemic Heart Disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, proinflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects (NIHD) and 86 individuals with IHD (aged 55 to 75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with no evidence of IHD (NIHD) (aged 65 to 96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (OR: 2.51, 95% CI: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia < 4log. No significant difference in cytokine production was observed between IHD patients and NIHD with TTV viremia ≥4log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4log displayed higher NLR and SIRI index than those with TTV viremia < 4log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented proinflammatory response and immunosenescence
{"title":"Association between TTV viremia, chronic inflammation, and ischemic heart disease risk: Insights from MARK-AGE and Report-Age projects","authors":"Robertina Giacconi, Francesco Piacenza, Fabrizio Maggi, Alexander Bürkle, María Moreno Villanueva, Lucia Mancinelli, Pietro Giorgio Spezia, Federica Novazzi, Francesca Drago Ferrante, Claudia Minosse, Paolo Antonio Grossi, Nicasio Mancini, Monia Cecati, Martijn E T Dollé, Eugène Jansen, Tilman Grune, Efstathios S Gonos, Claudio Franceschi, Miriam Capri, Birgit Weinberger, Ewa Sikora, Florence Debacq-Chainiaux, Wolfgang Stuetz, Mikko Hurme, P Eline Slagboom, Jürgen Bernhardt, Davide Gentilini, Luciano Calzari, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Fabrizia Lattanzio, Mauro Provinciali, Marco Malavolta","doi":"10.1093/gerona/glae228","DOIUrl":"https://doi.org/10.1093/gerona/glae228","url":null,"abstract":"The implication of Torquetenovirus (TTV) in Ischemic Heart Disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, proinflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects (NIHD) and 86 individuals with IHD (aged 55 to 75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with no evidence of IHD (NIHD) (aged 65 to 96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (OR: 2.51, 95% CI: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia &lt; 4log. No significant difference in cytokine production was observed between IHD patients and NIHD with TTV viremia ≥4log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4log displayed higher NLR and SIRI index than those with TTV viremia &lt; 4log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented proinflammatory response and immunosenescence","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489806","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}
Sarcopenia is recognized as a complex and multifactorial disorder that includes nutritional deficiency, inactivity, proinflammatory status, hormonal changes, neurological degeneration, and metabolic disturbances. Its' pathogenesis is not fully understood. Therefore, identifying specific biomarkers of sarcopenia will help us understand its pathophysiology. The most frequently reported blood-derived biomarkers of sarcopenia are growth factors, neuromuscular junctions, endocrine systems, mitochondrial dysfunction, inflammation-mediated and redox processes, muscle protein turnover, blood metabolomics, and behavior-mediated biomarkers. Here, we address the implications of sarcopenia biomarkers based on our research experience with KFACS cohort data. It includes free testosterone, myostatin, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF-15), procollagen type III N-terminal peptide (P3NP), creatinine-based biomarkers, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), brain-derived neurotrophic factor (BDNF), metabolites (proline, alanine, tryptophan), and multi-biomarker risk score. We attempted to explain the paradoxical findings of myostatin and FGF-21 levels in relation to sarcopenia. GDF-15 levels were associated with sarcopenia prevalence but not its incidence. Plasma P3NP and BDNF levels may be biomarkers of muscle quality rather than quantity. Lower erythrocyte EPA and DHA levels were associated with slow gait speed, and erythrocyte EPA levels were associated with low handgrip strength. We developed a multi-biomarker risk score for sarcopenia and found that its accuracy in diagnosing sarcopenia was higher than that of any single biomarker.
公认的 "肌肉疏松症 "是一种复杂的多因素疾病，包括营养缺乏、缺乏活动、促炎状态、荷尔蒙变化、神经退化和代谢紊乱。其发病机制尚不完全清楚。因此，确定肌肉疏松症的特定生物标志物将有助于我们了解其病理生理学。最常报道的肌肉疏松症血液生物标志物包括生长因子、神经肌肉接头、内分泌系统、线粒体功能障碍、炎症介导和氧化还原过程、肌肉蛋白质周转、血液代谢组学和行为介导的生物标志物。在此，我们将根据 KFACS 队列数据的研究经验，探讨肌肉疏松症生物标志物的影响。这些生物标志物包括游离睾酮、肌生成素、成纤维细胞生长因子 21 (FGF-21)、生长分化因子 15 (GDF-15)、胶原蛋白 III 型 N 端肽 (P3NP)、肌酐类生物标志物、二十碳五烯酸 (EPA) 和二十二碳六烯酸 (DHA)、脑源性神经营养因子 (BDNF)、代谢物（脯氨酸、丙氨酸、色氨酸）以及多重生物标志物风险评分。我们试图解释肌生成蛋白和成纤维细胞生长因子-21水平与肌肉疏松症相关的矛盾发现。GDF-15水平与肌肉疏松症患病率有关，但与发病率无关。血浆 P3NP 和 BDNF 水平可能是肌肉质量而非数量的生物标志物。红细胞 EPA 和 DHA 水平较低与步速缓慢有关，而红细胞 EPA 水平较低与手握力低有关。我们为肌少症制定了一个多生物标志物风险评分，发现其诊断肌少症的准确性高于任何单一生物标志物。
{"title":"From a solitary blood-derived biomarker to combined biomarkers of sarcopenia: Experiences from the Korean Frailty and Aging Cohort Study.","authors":"Chang Won Won,Miji Kim,Hyung Eun Shin","doi":"10.1093/gerona/glae237","DOIUrl":"https://doi.org/10.1093/gerona/glae237","url":null,"abstract":"Sarcopenia is recognized as a complex and multifactorial disorder that includes nutritional deficiency, inactivity, proinflammatory status, hormonal changes, neurological degeneration, and metabolic disturbances. Its' pathogenesis is not fully understood. Therefore, identifying specific biomarkers of sarcopenia will help us understand its pathophysiology. The most frequently reported blood-derived biomarkers of sarcopenia are growth factors, neuromuscular junctions, endocrine systems, mitochondrial dysfunction, inflammation-mediated and redox processes, muscle protein turnover, blood metabolomics, and behavior-mediated biomarkers. Here, we address the implications of sarcopenia biomarkers based on our research experience with KFACS cohort data. It includes free testosterone, myostatin, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF-15), procollagen type III N-terminal peptide (P3NP), creatinine-based biomarkers, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), brain-derived neurotrophic factor (BDNF), metabolites (proline, alanine, tryptophan), and multi-biomarker risk score. We attempted to explain the paradoxical findings of myostatin and FGF-21 levels in relation to sarcopenia. GDF-15 levels were associated with sarcopenia prevalence but not its incidence. Plasma P3NP and BDNF levels may be biomarkers of muscle quality rather than quantity. Lower erythrocyte EPA and DHA levels were associated with slow gait speed, and erythrocyte EPA levels were associated with low handgrip strength. We developed a multi-biomarker risk score for sarcopenia and found that its accuracy in diagnosing sarcopenia was higher than that of any single biomarker.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448062","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}
Brittney Lange-Maia, Tianhao Wang, Shahram Oveisgharan, Jeffrey M Hausdorff, David A Bennett, Aron S Buchman
Background Few studies have analyzed sensor-derived metrics of mobility abilities and total daily physical activity (TDPA). We tested whether sensor-derived mobility metrics and TDPA indices are independently associated with mobility disabilities. Methods This cohort study derived mobility abilities from a belt-worn sensor that recorded annual supervised gait testing. TDPA indices were obtained from a wrist-worn activity monitor. Mobility disability was determined by self-report and inability to perform an 8-feet walk task. Baseline associations of mobility metrics and TDPA (separately and together) were examined with logistic regressions and incident associations (average 7 years follow-up) with Cox models. Mediation analysis quantified the extent mobility metrics mediate the association of TDPA with mobility disability. Results 724 ambulatory older adults (mean age 82 years, 77.4% female) were studied. In separate models, mobility abilities (e.g. step time variability, turning angular velocity) and TDPA were related to mobility disabilities. Examined together in a single model, mobility abilities remained associated with mobility disabilities, while TDPA was attenuated. This attenuation of TDPA could be explained by mediation analysis that showed about 50% of TDPA associations with mobility disabilities is mediated via mobility abilities (prevalent mobility disability 54%, incident mobility disability 40%, incident loss of ambulation 50%; all p’s<0.001). Conclusions Sensor-derived mobility metrics assess more diverse facets of mobility. These metrics mediate approximately half of the association of higher levels of daily physical activity with reduced mobility disability in older adults. Findings may inform the design of targeted interventions to reduce mobility disability in late life.
{"title":"Mobility abilities mediate the association of a more active lifestyle with mobility disability in older adults","authors":"Brittney Lange-Maia, Tianhao Wang, Shahram Oveisgharan, Jeffrey M Hausdorff, David A Bennett, Aron S Buchman","doi":"10.1093/gerona/glae238","DOIUrl":"https://doi.org/10.1093/gerona/glae238","url":null,"abstract":"Background Few studies have analyzed sensor-derived metrics of mobility abilities and total daily physical activity (TDPA). We tested whether sensor-derived mobility metrics and TDPA indices are independently associated with mobility disabilities. Methods This cohort study derived mobility abilities from a belt-worn sensor that recorded annual supervised gait testing. TDPA indices were obtained from a wrist-worn activity monitor. Mobility disability was determined by self-report and inability to perform an 8-feet walk task. Baseline associations of mobility metrics and TDPA (separately and together) were examined with logistic regressions and incident associations (average 7 years follow-up) with Cox models. Mediation analysis quantified the extent mobility metrics mediate the association of TDPA with mobility disability. Results 724 ambulatory older adults (mean age 82 years, 77.4% female) were studied. In separate models, mobility abilities (e.g. step time variability, turning angular velocity) and TDPA were related to mobility disabilities. Examined together in a single model, mobility abilities remained associated with mobility disabilities, while TDPA was attenuated. This attenuation of TDPA could be explained by mediation analysis that showed about 50% of TDPA associations with mobility disabilities is mediated via mobility abilities (prevalent mobility disability 54%, incident mobility disability 40%, incident loss of ambulation 50%; all p’s&lt;0.001). Conclusions Sensor-derived mobility metrics assess more diverse facets of mobility. These metrics mediate approximately half of the association of higher levels of daily physical activity with reduced mobility disability in older adults. Findings may inform the design of targeted interventions to reduce mobility disability in late life.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328774","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}
The relationship between pain and falls remains controversial. Therefore, this study explored the associations between pain and fall-related outcomes in 5,340 middle-aged (45–65 years) adults residing in the communities in Korea. Pain was defined as pain at any location, pain-related activity restriction (PAR), and persistent pain. The outcome measures included fall injuries, recurrent falls, injurious falls, and fall-related hip fractures. A multivariate logistic regression model was used to examine the relationship between pain and fall outcome. Among the study participants, 54.0% reported having experienced pain. During a follow-up period of up to 14 years, those who reported pain and PAR at baseline exhibited a positive association with the occurrence of fall injury (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.27–2.53) and injurious falls (OR 1.72, 95% CI 1.20–2.48) but not with recurrent falls (OR 1.90, 95% CI 0.80–4.54). We also observed a positive association between persistent pain and the risk of fall injury (OR 1.41, 95% CI 1.13–1.91), whereas no consistent conclusions were drawn regarding the risk of recurrent falls and injurious falls. We also did not identify any correlation between pain and hip fractures resulting from falls. In conclusion, our findings of the positive correlations of pain and PAR at baseline with fall injuries and injurious falls but not recurrent falls during follow-up suggest that public health initiatives should prioritize pain screening, especially for participants reporting ankle and toe pain, and implement suitable interventions to mitigate the risk of falls and the associated adverse outcomes among middle-aged adults.
疼痛与跌倒之间的关系仍存在争议。因此，本研究以居住在韩国社区的 5340 名中年人（45-65 岁）为对象，探讨了疼痛与跌倒相关结果之间的关系。疼痛被定义为任何部位的疼痛、与疼痛相关的活动限制（PAR）和持续性疼痛。结果测量包括跌倒伤害、复发性跌倒、伤害性跌倒和与跌倒相关的髋部骨折。研究采用多变量逻辑回归模型来检验疼痛与跌倒结果之间的关系。在研究参与者中，54.0%的人表示曾经历过疼痛。在长达 14 年的随访期间，基线时报告疼痛和 PAR 的人与跌倒伤害的发生（几率比 [OR] 1.79，95% 置信区间 [CI] 1.27-2.53）和伤害性跌倒（OR 1.72，95% CI 1.20-2.48）呈正相关，但与复发性跌倒（OR 1.90，95% CI 0.80-4.54）无关。我们还观察到持续性疼痛与跌倒受伤风险之间存在正相关关系（OR 1.41，95% CI 1.13-1.91），而对于反复跌倒和伤害性跌倒的风险则没有得出一致的结论。我们也没有发现疼痛与跌倒导致的髋部骨折之间存在任何相关性。总之，我们的研究结果表明，基线疼痛和PAR与跌倒受伤和伤害性跌倒呈正相关，但与随访期间的复发性跌倒无关，这表明公共卫生活动应优先考虑疼痛筛查，尤其是对报告脚踝和脚趾疼痛的参与者，并实施适当的干预措施，以降低中年人跌倒的风险和相关的不良后果。
{"title":"Association of pain with falls and fractures among middle-aged Korean community-dwelling adults","authors":"Shaoli Yao, Xi-wen Chen","doi":"10.1093/gerona/glae241","DOIUrl":"https://doi.org/10.1093/gerona/glae241","url":null,"abstract":"The relationship between pain and falls remains controversial. Therefore, this study explored the associations between pain and fall-related outcomes in 5,340 middle-aged (45–65 years) adults residing in the communities in Korea. Pain was defined as pain at any location, pain-related activity restriction (PAR), and persistent pain. The outcome measures included fall injuries, recurrent falls, injurious falls, and fall-related hip fractures. A multivariate logistic regression model was used to examine the relationship between pain and fall outcome. Among the study participants, 54.0% reported having experienced pain. During a follow-up period of up to 14 years, those who reported pain and PAR at baseline exhibited a positive association with the occurrence of fall injury (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.27–2.53) and injurious falls (OR 1.72, 95% CI 1.20–2.48) but not with recurrent falls (OR 1.90, 95% CI 0.80–4.54). We also observed a positive association between persistent pain and the risk of fall injury (OR 1.41, 95% CI 1.13–1.91), whereas no consistent conclusions were drawn regarding the risk of recurrent falls and injurious falls. We also did not identify any correlation between pain and hip fractures resulting from falls. In conclusion, our findings of the positive correlations of pain and PAR at baseline with fall injuries and injurious falls but not recurrent falls during follow-up suggest that public health initiatives should prioritize pain screening, especially for participants reporting ankle and toe pain, and implement suitable interventions to mitigate the risk of falls and the associated adverse outcomes among middle-aged adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325345","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}
Eduardo L Cadore, Mikel Izquierdo, Nicolás Martínez-Velilla, Eduarda Blanco-Rambo, Fabricio Zambom-Ferraresi, Mikel L Sáez de Asteasu
Background This study aimed to determine the threshold of muscle power and strength enhancements that lead to functional gains after exercise intervention in an acute care unit. Methods A total of 302 older patients (intervention: 169, control: 133) from two randomized clinical trials were included (mean age 86.7 years). We measured maximal strength (1RM) and muscle power via a velocity transducer during leg press exercise at 30% and 60% of 1RM. A multicomponent exercise program, including power training, balance, and gait exercises performed over 3 to 6 consecutive days, served as the intervention. We used an anchor-based method to correlate muscle function increases with the Short Physical Performance Battery (SPPB) and gait velocity (GVT) to define clinically meaningful improvements (CMI). Results In the intervention group, marked differences were found in maximal power at 30% of 1RM between SPPB responders and non-responders (relative 83.5% vs. 34.8%; absolute 33.0 vs. 12.8 W; P<0.05) and at 60% of 1RM (relative 61.1% vs. 22.4%; P<0.05). GVT responders demonstrated significantly greater improvements in both relative and absolute maximal power than non-responders at both 30% and 60% of 1RM (P<0.05), as well as greater absolute 1RM gains (21.2 vs. 15.2 kg, P<0.05). CMI for muscle power based on SPPB and GVT ranged from 30.2% to 48.7%, whereas for 1RM, it was 8.2% based on GVT. Conclusion Muscle power gains were most notable in patients with improvements in the SPPB and GVT, highlighting the critical role of muscle power in functional recovery in these patients.
{"title":"Identifying clinically meaningful muscle power enhancements and their functional correlates in hospitalized older patients","authors":"Eduardo L Cadore, Mikel Izquierdo, Nicolás Martínez-Velilla, Eduarda Blanco-Rambo, Fabricio Zambom-Ferraresi, Mikel L Sáez de Asteasu","doi":"10.1093/gerona/glae240","DOIUrl":"https://doi.org/10.1093/gerona/glae240","url":null,"abstract":"Background This study aimed to determine the threshold of muscle power and strength enhancements that lead to functional gains after exercise intervention in an acute care unit. Methods A total of 302 older patients (intervention: 169, control: 133) from two randomized clinical trials were included (mean age 86.7 years). We measured maximal strength (1RM) and muscle power via a velocity transducer during leg press exercise at 30% and 60% of 1RM. A multicomponent exercise program, including power training, balance, and gait exercises performed over 3 to 6 consecutive days, served as the intervention. We used an anchor-based method to correlate muscle function increases with the Short Physical Performance Battery (SPPB) and gait velocity (GVT) to define clinically meaningful improvements (CMI). Results In the intervention group, marked differences were found in maximal power at 30% of 1RM between SPPB responders and non-responders (relative 83.5% vs. 34.8%; absolute 33.0 vs. 12.8 W; P&lt;0.05) and at 60% of 1RM (relative 61.1% vs. 22.4%; P&lt;0.05). GVT responders demonstrated significantly greater improvements in both relative and absolute maximal power than non-responders at both 30% and 60% of 1RM (P&lt;0.05), as well as greater absolute 1RM gains (21.2 vs. 15.2 kg, P&lt;0.05). CMI for muscle power based on SPPB and GVT ranged from 30.2% to 48.7%, whereas for 1RM, it was 8.2% based on GVT. Conclusion Muscle power gains were most notable in patients with improvements in the SPPB and GVT, highlighting the critical role of muscle power in functional recovery in these patients.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"227 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325479","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}
BACKGROUNDPerson-centered approaches to measuring severity of multimorbidity (≥ 2 chronic conditions) can help clinicians assess the individual experience of multimorbidity and inform effective caregiving and intervention strategies. We examine how limitations in everyday activities attributable to specific chronic conditions act independently and in tandem to influence individual perceptions of multimorbidity severity.METHODSData from the Panel Study of Income Dynamics (2005-2021) were used to investigate self-reported limitations in normal daily activities resulting from nine chronic conditions (hypertension, arthritis, diabetes, heart condition [heart disease/heart attack], cancer, lung disease, stroke, depression, and memory loss) in 4,318 adults aged 55-95 (18,878 person-wave observations). We used descriptive and inferential analyses to estimate limitations resulting from specific conditions, limitations attributable to condition combinations, and the contribution of comorbid conditions to condition-specific and overall severity. Follow-up analyses addressed mortality selection using inverse probability weighting (IPW) and examined cancer type and cancer status/treatment modality among respondents reporting cancer diagnosis.RESULTSOf the more prevalent conditions, arthritis was associated with the most severe limitations to normal activities. Memory loss was the least frequent condition reported, but resulted in the most severe limitations, and as a comorbid condition, increased limitations reported for most conditions. IPW adjusted models revealed heterogeneity in estimates for some conditions including cancer and cancer survivors tended to report less lethal cancers that were cured or in remission.CONCLUSIONSOur results suggest that efforts to prevent and treat arthritis and support cognitive function may reduce the severity of multimorbidity experienced by the individual.
{"title":"Exploring Perceived Limitations to Daily Activities Due to Chronic Conditions: A Person-Centered Approach to Measuring Multimorbidity Severity.","authors":"Nicholas Bishop,Corey Nagel,Ana R Quiñones","doi":"10.1093/gerona/glae239","DOIUrl":"https://doi.org/10.1093/gerona/glae239","url":null,"abstract":"BACKGROUNDPerson-centered approaches to measuring severity of multimorbidity (≥ 2 chronic conditions) can help clinicians assess the individual experience of multimorbidity and inform effective caregiving and intervention strategies. We examine how limitations in everyday activities attributable to specific chronic conditions act independently and in tandem to influence individual perceptions of multimorbidity severity.METHODSData from the Panel Study of Income Dynamics (2005-2021) were used to investigate self-reported limitations in normal daily activities resulting from nine chronic conditions (hypertension, arthritis, diabetes, heart condition [heart disease/heart attack], cancer, lung disease, stroke, depression, and memory loss) in 4,318 adults aged 55-95 (18,878 person-wave observations). We used descriptive and inferential analyses to estimate limitations resulting from specific conditions, limitations attributable to condition combinations, and the contribution of comorbid conditions to condition-specific and overall severity. Follow-up analyses addressed mortality selection using inverse probability weighting (IPW) and examined cancer type and cancer status/treatment modality among respondents reporting cancer diagnosis.RESULTSOf the more prevalent conditions, arthritis was associated with the most severe limitations to normal activities. Memory loss was the least frequent condition reported, but resulted in the most severe limitations, and as a comorbid condition, increased limitations reported for most conditions. IPW adjusted models revealed heterogeneity in estimates for some conditions including cancer and cancer survivors tended to report less lethal cancers that were cured or in remission.CONCLUSIONSOur results suggest that efforts to prevent and treat arthritis and support cognitive function may reduce the severity of multimorbidity experienced by the individual.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320989","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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