Hillary J Rouse, Zahinoor Ismail, Ross Andel, Victor A Molinari, John A Schinka, Brent J Small
Background: To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI).
Methods: Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer's Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed.
Results: Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time.
Conclusions: This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition.
背景:研究认知能力健康或患有轻度认知障碍(MCI)的老年人在认知能力方面的横向差异和纵向变化:对国家阿尔茨海默氏症协调中心数据库中认知健康(11 771 人)或确诊为 MCI(5 520 人)的参与者(17 291 人)进行二次数据分析。总体而言,24.7% 的样本符合 MBI 标准。认知能力通过神经心理学电池进行检查,该电池可评估注意力、外显记忆、执行功能、语言、视觉空间能力和处理速度:结果:患有肌肉萎缩性脑损伤的老年人,无论其认知能力健康与否,在注意力、外显记忆、执行功能、语言和处理速度等任务上的基线表现都明显较差,而且在注意力、外显记忆、语言和处理速度等任务上的纵向下降幅度更大。患有 MBI 的认知健康老年人在基线视觉空间能力任务和处理速度任务上的表现明显差于未患有 MBI 的认知健康老年人。患有MCI和MBI的老年人在基线执行功能、视觉空间能力和跨时间处理速度任务上的表现明显差于仅患有MCI的老年人:本研究发现,有证据表明,MBI 与较差的认知表现有横向和纵向关系。此外,MBI 和 MCI 患者在多项认知任务上的表现在横向和纵向上都较差。这些结果支持MBI与认知的不同方面有独特的关联。
{"title":"Impact of Mild Behavioral Impairment on Longitudinal Changes in Cognition.","authors":"Hillary J Rouse, Zahinoor Ismail, Ross Andel, Victor A Molinari, John A Schinka, Brent J Small","doi":"10.1093/gerona/glad098","DOIUrl":"10.1093/gerona/glad098","url":null,"abstract":"<p><strong>Background: </strong>To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI).</p><p><strong>Methods: </strong>Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer's Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed.</p><p><strong>Results: </strong>Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time.</p><p><strong>Conclusions: </strong>This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9289499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angéline Galvin, Jacob Krabbe Pedersen, Mary K Wojczynski, Svetlana Ukraintseva, Konstantin Arbeev, Mary Feitosa, Michael A Province, Kaare Christensen
Background: A recent study suggested that the protective effect of familial longevity becomes negligible for centenarians. However, the authors assessed the dependence on familial longevity in centenarians by comparing centenarians with 1 parent surviving to age 80+ to centenarians whose same-sexed parent did not survive to age 80. Here we test whether the protective effect of familial longevity persists after age 100 using more restrictive definitions of long-lived families.
Methods: Long-lived sibships were identified through 3 nationwide, consecutive studies in Denmark, including families with either at least 2 siblings aged 90+ or a Family Longevity Selection Score (FLoSS) above 7. Long-lived siblings enrolled in these studies and who reached age 100 were included. For each sibling, 5 controls matched on sex and year of birth were randomly selected among centenarians in the Danish population. Survival time from age 100 was described with Kaplan-Meier curves for siblings and controls separately. Survival analyses were performed using stratified Cox proportional hazards models.
Results: A total of 340 individuals from long-lived sibships who survived to age 100 and 1 700 controls were included. Among the long-lived siblings and controls, 1 650 (81%) were women. The results showed that long-lived siblings presented better overall survival after age 100 than sporadic long-livers (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.71-0.91), with even lower estimate (HR = 0.65, 95% CI = 0.50-0.85) if familial longevity was defined by FLoSS.
Conclusions: The present study, with virtually no loss to follow-up, demonstrated a persistence of protective effect of familial longevity after age 100.
{"title":"The Protective Effect of Familial Longevity Persists After Age 100: Findings From the Danish National Registers.","authors":"Angéline Galvin, Jacob Krabbe Pedersen, Mary K Wojczynski, Svetlana Ukraintseva, Konstantin Arbeev, Mary Feitosa, Michael A Province, Kaare Christensen","doi":"10.1093/gerona/glad164","DOIUrl":"10.1093/gerona/glad164","url":null,"abstract":"<p><strong>Background: </strong>A recent study suggested that the protective effect of familial longevity becomes negligible for centenarians. However, the authors assessed the dependence on familial longevity in centenarians by comparing centenarians with 1 parent surviving to age 80+ to centenarians whose same-sexed parent did not survive to age 80. Here we test whether the protective effect of familial longevity persists after age 100 using more restrictive definitions of long-lived families.</p><p><strong>Methods: </strong>Long-lived sibships were identified through 3 nationwide, consecutive studies in Denmark, including families with either at least 2 siblings aged 90+ or a Family Longevity Selection Score (FLoSS) above 7. Long-lived siblings enrolled in these studies and who reached age 100 were included. For each sibling, 5 controls matched on sex and year of birth were randomly selected among centenarians in the Danish population. Survival time from age 100 was described with Kaplan-Meier curves for siblings and controls separately. Survival analyses were performed using stratified Cox proportional hazards models.</p><p><strong>Results: </strong>A total of 340 individuals from long-lived sibships who survived to age 100 and 1 700 controls were included. Among the long-lived siblings and controls, 1 650 (81%) were women. The results showed that long-lived siblings presented better overall survival after age 100 than sporadic long-livers (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.71-0.91), with even lower estimate (HR = 0.65, 95% CI = 0.50-0.85) if familial longevity was defined by FLoSS.</p><p><strong>Conclusions: </strong>The present study, with virtually no loss to follow-up, demonstrated a persistence of protective effect of familial longevity after age 100.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jorge R Kizer, Sheena Patel, Peter Ganz, Anne B Newman, Shalender Bhasin, Se-Jin Lee, Peggy M Cawthon, Nathan K LeBrasseur, Sanjiv J Shah, Bruce M Psaty, Russell P Tracy, Steven R Cummings
Background: Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.
Methods: We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography-tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults.
Results: In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function.
Conclusions: Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.
{"title":"Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.","authors":"Jorge R Kizer, Sheena Patel, Peter Ganz, Anne B Newman, Shalender Bhasin, Se-Jin Lee, Peggy M Cawthon, Nathan K LeBrasseur, Sanjiv J Shah, Bruce M Psaty, Russell P Tracy, Steven R Cummings","doi":"10.1093/gerona/glad206","DOIUrl":"10.1093/gerona/glad206","url":null,"abstract":"<p><strong>Background: </strong>Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.</p><p><strong>Methods: </strong>We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography-tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults.</p><p><strong>Results: </strong>In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function.</p><p><strong>Conclusions: </strong>Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10538157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaqueline Aragoni da Silva, Laurent O Martinez, Yves Rolland, Souad Najib, Mikaël Croyal, Bertrand Perret, Nabila Jabrane-Ferrat, Hicham El Costa, Sophie Guyonnet, Bruno Vellas, Philipe de Souto Barreto
Background: Intrinsic capacity (IC) is a concept related to functionality that reflects healthy aging. ATPase inhibitory factor 1 (IF1) is a multifaceted protein that regulates mitochondrial oxidative phosphorylation (OXPHOS), and may be involved in IC. The objective of this study is to investigate the association between plasma levels of IF1 and IC changes in community-dwelling older adults.
Methods: Community-dwelling older adults from the Multidomain Alzheimer Preventive Trial (MAPT Study) were enrolled in this study. A composite IC score was calculated based on 4 IC domains: locomotion, psychological dimension, cognition, and vitality (with data available annually over 4 years of follow-up). Secondary analyses were conducted on the sensory domain (with data available only for 1 year of follow-up). Mixed-model linear regression adjusted for confounders was conducted.
Results: A total of 1 090 participants with usable IF1 values were included in the study (75.3 ± 4.4 years; 64% females). Compared to the lowest quartile, both the low- and high-intermediate IF1 quartiles were found to be cross-sectionally associated with greater composite IC scores across 4 domains (βlow-intermediate, 1.33; 95% confidence interval [CI] 0.06-2.60 and βhigh-intermediate, 1.78; 95% CI 0.49-3.06). In the secondary analyses, the highest quartile was found to be associated with a slower decline in composite IC scores across 5 domains over 1 year (βhigh 1.60; 95% CI 0.06-3.15). The low- and high-intermediate IF1 quartiles were also found to be cross-sectionally associated with greater locomotion (βlow-intermediate, 2.72; 95% CI 0.36-5.08) and vitality scores (βhigh-intermediate, 1.59; 95% CI 0.06-3.12), respectively.
Conclusions: This study is the first to demonstrate that levels of circulating IF1, a mitochondrial-related biomarker, are associated with IC composite scores in both cross-sectional and prospective analyses among community-dwelling older adults. However, further research is needed to confirm these findings and elucidate the potential underlying mechanisms that may explain these associations.
背景:内在能力(IC)是一个与反映健康老化的功能有关的概念。ATPase抑制因子1(IF1)是一种调节线粒体氧化磷酸化(OXPHOS)的多层面蛋白质,可能与IC有关。本研究旨在调查社区老年人血浆中 IF1 水平与 IC 变化之间的关系:方法:本研究招募了来自多领域阿尔茨海默氏症预防试验(MAPT 研究)的社区老年人。根据 4 个 IC 领域:运动、心理层面、认知和活力(在 4 年的随访中每年提供数据)计算 IC 综合得分。对感觉领域进行了二次分析(仅有 1 年的随访数据)。对混杂因素进行了混合模型线性回归分析:研究共纳入了 1 090 名具有可用 IF1 值的参与者(75.3 ± 4.4 岁;64% 为女性)。与最低四分位数相比,IF1 低中级和高中级四分位数均与 4 个领域的 IC 综合得分较高有关(β 低中级,1.33;95% 置信区间 [CI],0.06-2.60;β 高中级,1.78;95% 置信区间,0.49-3.06)。在二次分析中发现,最高四分位数与 1 年内 5 个领域 IC 综合评分下降较慢有关(β高 1.60;95% CI 0.06-3.15)。研究还发现,IF1中级偏低和偏高四分位数分别与更高的运动能力(β低-中级,2.72;95% CI 0.36-5.08)和活力得分(β高-中级,1.59;95% CI 0.06-3.12)横截面相关:本研究首次证明,在对社区居住的老年人进行横断面和前瞻性分析时,与线粒体相关的生物标志物循环 IF1 的水平与 IC 综合评分相关。然而,还需要进一步的研究来证实这些发现,并阐明可能解释这些关联的潜在内在机制。
{"title":"Plasma Level of ATPase Inhibitory Factor 1 and Intrinsic Capacity in Community-Dwelling Older Adults: Prospective Data From the MAPT Study.","authors":"Jaqueline Aragoni da Silva, Laurent O Martinez, Yves Rolland, Souad Najib, Mikaël Croyal, Bertrand Perret, Nabila Jabrane-Ferrat, Hicham El Costa, Sophie Guyonnet, Bruno Vellas, Philipe de Souto Barreto","doi":"10.1093/gerona/glad142","DOIUrl":"10.1093/gerona/glad142","url":null,"abstract":"<p><strong>Background: </strong>Intrinsic capacity (IC) is a concept related to functionality that reflects healthy aging. ATPase inhibitory factor 1 (IF1) is a multifaceted protein that regulates mitochondrial oxidative phosphorylation (OXPHOS), and may be involved in IC. The objective of this study is to investigate the association between plasma levels of IF1 and IC changes in community-dwelling older adults.</p><p><strong>Methods: </strong>Community-dwelling older adults from the Multidomain Alzheimer Preventive Trial (MAPT Study) were enrolled in this study. A composite IC score was calculated based on 4 IC domains: locomotion, psychological dimension, cognition, and vitality (with data available annually over 4 years of follow-up). Secondary analyses were conducted on the sensory domain (with data available only for 1 year of follow-up). Mixed-model linear regression adjusted for confounders was conducted.</p><p><strong>Results: </strong>A total of 1 090 participants with usable IF1 values were included in the study (75.3 ± 4.4 years; 64% females). Compared to the lowest quartile, both the low- and high-intermediate IF1 quartiles were found to be cross-sectionally associated with greater composite IC scores across 4 domains (βlow-intermediate, 1.33; 95% confidence interval [CI] 0.06-2.60 and βhigh-intermediate, 1.78; 95% CI 0.49-3.06). In the secondary analyses, the highest quartile was found to be associated with a slower decline in composite IC scores across 5 domains over 1 year (βhigh 1.60; 95% CI 0.06-3.15). The low- and high-intermediate IF1 quartiles were also found to be cross-sectionally associated with greater locomotion (βlow-intermediate, 2.72; 95% CI 0.36-5.08) and vitality scores (βhigh-intermediate, 1.59; 95% CI 0.06-3.12), respectively.</p><p><strong>Conclusions: </strong>This study is the first to demonstrate that levels of circulating IF1, a mitochondrial-related biomarker, are associated with IC composite scores in both cross-sectional and prospective analyses among community-dwelling older adults. However, further research is needed to confirm these findings and elucidate the potential underlying mechanisms that may explain these associations.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashley K Brown, Daniel L Mazula, Lori Roberts, Carolyn Roos, Bin Zhang, Vesselina M Pearsall, Marissa J Schafer, Thomas A White, Runqing Huang, Navasuja Kumar, Jordan D Miller, Richard A Miller, Nathan K LeBrasseur
Dynamic measures of resilience-the ability to resist and recover from a challenge-may be informative of the rate of aging before overt manifestations such as chronic disease, disability, and frailty. From this perspective mid-life resilience may predict longevity and late-life health. To test this hypothesis, we developed simple, reproducible, clinically relevant challenges, and outcome measures of physical resilience that revealed differences between and within age groups of genetically heterogeneous mice, and then examined associations between mid-life resilience and both lifespan and late-life measures of physiological function. We demonstrate that time to recovery from isoflurane anesthesia and weight change following a regimen of chemotherapy significantly differed among young, middle-aged, and older mice, and were more variable in older mice. Females that recovered faster than the median time from anesthesia (more resilient) at 12 months of age lived 8% longer than their counterparts, while more resilient males in mid-life exhibited better cardiac (fractional shortening and left ventricular volumes) and metabolic (glucose tolerance) function at 24 months of age. Moreover, female mice with less than the median weight loss at Day 3 of the cisplatin challenge lived 8% longer than those that lost more weight. In contrast, females who had more weight loss between Days 15 and 20 were relatively protected against early death. These data suggest that measures of physical resilience in mid-life may provide information about individual differences in aging, lifespan, and key parameters of late-life health.
{"title":"Physical Resilience as a Predictor of Lifespan and Late-Life Health in Genetically Heterogeneous Mice.","authors":"Ashley K Brown, Daniel L Mazula, Lori Roberts, Carolyn Roos, Bin Zhang, Vesselina M Pearsall, Marissa J Schafer, Thomas A White, Runqing Huang, Navasuja Kumar, Jordan D Miller, Richard A Miller, Nathan K LeBrasseur","doi":"10.1093/gerona/glad207","DOIUrl":"10.1093/gerona/glad207","url":null,"abstract":"<p><p>Dynamic measures of resilience-the ability to resist and recover from a challenge-may be informative of the rate of aging before overt manifestations such as chronic disease, disability, and frailty. From this perspective mid-life resilience may predict longevity and late-life health. To test this hypothesis, we developed simple, reproducible, clinically relevant challenges, and outcome measures of physical resilience that revealed differences between and within age groups of genetically heterogeneous mice, and then examined associations between mid-life resilience and both lifespan and late-life measures of physiological function. We demonstrate that time to recovery from isoflurane anesthesia and weight change following a regimen of chemotherapy significantly differed among young, middle-aged, and older mice, and were more variable in older mice. Females that recovered faster than the median time from anesthesia (more resilient) at 12 months of age lived 8% longer than their counterparts, while more resilient males in mid-life exhibited better cardiac (fractional shortening and left ventricular volumes) and metabolic (glucose tolerance) function at 24 months of age. Moreover, female mice with less than the median weight loss at Day 3 of the cisplatin challenge lived 8% longer than those that lost more weight. In contrast, females who had more weight loss between Days 15 and 20 were relatively protected against early death. These data suggest that measures of physical resilience in mid-life may provide information about individual differences in aging, lifespan, and key parameters of late-life health.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10215321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaomeng Chen, Nadia M Chu, Valerie Thompson, Evelien E Quint, Sami Alasfar, Qian-Li Xue, Daniel C Brennan, Silas P Norman, Bonnie E Lonze, Jeremy D Walston, Dorry L Segev, Mara A McAdams-DeMarco
Background: Frailty is associated with poor outcomes in surgical patients including kidney transplant (KT) recipients. Transplant centers that measure frailty have better pre- and postoperative outcomes. However, clinical utility of existing tools is low due to time constraints. To address this major barrier to implementation in the preoperative evaluation of patients, we developed an abridged frailty phenotype.
Methods: The abridged frailty phenotype was developed by simplifying the 5 physical frailty phenotype (PFP) components in a two-center prospective cohort of 3 220 KT candidates and tested for efficiency (time to completion) in 20 candidates evaluation (January 2009 to March 2020). We examined area under curve (AUC) and Cohen's kappa agreement to compare the abridged assessment with the PFP. We compared waitlist mortality risk (competing risks models) by frailty using the PFP and abridged assessment, respectively. Model discrimination was assessed using Harrell's C-statistic.
Results: Of 3 220 candidates, the PFP and abridged assessment identified 23.8% and 27.4% candidates as frail, respectively. The abridged frailty phenotype had substantial agreement (kappa = 0.69, 95% CI: 0.66-0.71) and excellent discrimination (AUC = 0.861). Among 20 patients at evaluation, abridged assessment took 5-7 minutes to complete. The PFP and abridged assessment had similar associations with waitlist mortality (subdistribution hazard ratio [SHR] = 1.62, 95% CI: 1.26-2.08 vs SHR = 1.70, 95% CI: 1.33-2.16) and comparable mortality discrimination (p = .51).
Conclusions: The abridged assessment is an efficient and valid way to identify frailty. It predicts waitlist mortality without sacrificing discrimination. Surgical departments should consider utilizing the abridged assessment to evaluate frailty in patients when time is limited.
{"title":"Development and Validation of an Abridged Physical Frailty Phenotype for Clinical Use: A Cohort Study Among Kidney Transplant Candidates.","authors":"Xiaomeng Chen, Nadia M Chu, Valerie Thompson, Evelien E Quint, Sami Alasfar, Qian-Li Xue, Daniel C Brennan, Silas P Norman, Bonnie E Lonze, Jeremy D Walston, Dorry L Segev, Mara A McAdams-DeMarco","doi":"10.1093/gerona/glad173","DOIUrl":"10.1093/gerona/glad173","url":null,"abstract":"<p><strong>Background: </strong>Frailty is associated with poor outcomes in surgical patients including kidney transplant (KT) recipients. Transplant centers that measure frailty have better pre- and postoperative outcomes. However, clinical utility of existing tools is low due to time constraints. To address this major barrier to implementation in the preoperative evaluation of patients, we developed an abridged frailty phenotype.</p><p><strong>Methods: </strong>The abridged frailty phenotype was developed by simplifying the 5 physical frailty phenotype (PFP) components in a two-center prospective cohort of 3 220 KT candidates and tested for efficiency (time to completion) in 20 candidates evaluation (January 2009 to March 2020). We examined area under curve (AUC) and Cohen's kappa agreement to compare the abridged assessment with the PFP. We compared waitlist mortality risk (competing risks models) by frailty using the PFP and abridged assessment, respectively. Model discrimination was assessed using Harrell's C-statistic.</p><p><strong>Results: </strong>Of 3 220 candidates, the PFP and abridged assessment identified 23.8% and 27.4% candidates as frail, respectively. The abridged frailty phenotype had substantial agreement (kappa = 0.69, 95% CI: 0.66-0.71) and excellent discrimination (AUC = 0.861). Among 20 patients at evaluation, abridged assessment took 5-7 minutes to complete. The PFP and abridged assessment had similar associations with waitlist mortality (subdistribution hazard ratio [SHR] = 1.62, 95% CI: 1.26-2.08 vs SHR = 1.70, 95% CI: 1.33-2.16) and comparable mortality discrimination (p = .51).</p><p><strong>Conclusions: </strong>The abridged assessment is an efficient and valid way to identify frailty. It predicts waitlist mortality without sacrificing discrimination. Surgical departments should consider utilizing the abridged assessment to evaluate frailty in patients when time is limited.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10440338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vidyulata Kamath, Kening Jiang, Kevin J Manning, R Scott Mackin, Keenan A Walker, Danielle Powell, Frank R Lin, Honglei Chen, Willa D Brenowitz, Kristine Yaffe, Eleanor M Simonsick, Jennifer A Deal
Background: We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators.
Methods: Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships.
Results: Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity.
Conclusions: Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.
{"title":"Olfactory Dysfunction and Depression Trajectories in Community-Dwelling Older Adults.","authors":"Vidyulata Kamath, Kening Jiang, Kevin J Manning, R Scott Mackin, Keenan A Walker, Danielle Powell, Frank R Lin, Honglei Chen, Willa D Brenowitz, Kristine Yaffe, Eleanor M Simonsick, Jennifer A Deal","doi":"10.1093/gerona/glad139","DOIUrl":"10.1093/gerona/glad139","url":null,"abstract":"<p><strong>Background: </strong>We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators.</p><p><strong>Methods: </strong>Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships.</p><p><strong>Results: </strong>Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity.</p><p><strong>Conclusions: </strong>Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Air Pollution: A Pressing Threat to Functioning in the Older Adults.","authors":"Zilong Zhang, Hualiang Lin","doi":"10.1093/gerona/glad145","DOIUrl":"10.1093/gerona/glad145","url":null,"abstract":"","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":"2307-2308"},"PeriodicalIF":5.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad A B S Akhonda, Mary E Faulkner, Zhaoyuan Gong, John P Laporte, Sarah Church, Jarod D'Agostino, Jan Bergeron, Christopher M Bergeron, Luigi Ferrucci, Mustapha Bouhrara
The brainstem functions as a relay and integrative brain center and plays an essential role in motor function. Whether brainstem tissue deterioration, including demyelination, affects motor function has not been studied. Understanding the potential relationship between brainstem demyelination and motor function may be useful for the early diagnosis of neurodegenerative diseases and to understand age-related gait impairments that have no apparent cause. In this work, we investigated the associations between rapid or usual gait speeds, as integrative measures of motor function, and cerebral myelin content. In 118 individuals (age 22-94 years) free of neurodegenerative diseases or cognitive impairment, myelin content was assessed as the myelin water fraction, a direct magnetic resonance imaging measure of myelin content, and longitudinal and transverse relaxation rates (R1 and R2), which are sensitive magnetic resonance imaging measures of myelin content. Our results indicate that participants with lower usual or rapid gait speed exhibited lower values of myelin water fraction and R1 in the main brainstem regions, which were more evident and statistically significant in the midbrain. In contrast, we found no significant associations between gait speeds and R2, an expected result because various physiological factors confound R2. These original findings provide evidence that the level of brainstem myelination may affect gait performance among cognitively unimpaired adults who are free from any clinically detectable neurodegenerative diseases. Further studies are needed to understand the longitudinal changes in brainstem myelination with aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.
{"title":"The Effect of the Human Brainstem Myelination on Gait Speed in Normative Aging.","authors":"Mohammad A B S Akhonda, Mary E Faulkner, Zhaoyuan Gong, John P Laporte, Sarah Church, Jarod D'Agostino, Jan Bergeron, Christopher M Bergeron, Luigi Ferrucci, Mustapha Bouhrara","doi":"10.1093/gerona/glad193","DOIUrl":"10.1093/gerona/glad193","url":null,"abstract":"<p><p>The brainstem functions as a relay and integrative brain center and plays an essential role in motor function. Whether brainstem tissue deterioration, including demyelination, affects motor function has not been studied. Understanding the potential relationship between brainstem demyelination and motor function may be useful for the early diagnosis of neurodegenerative diseases and to understand age-related gait impairments that have no apparent cause. In this work, we investigated the associations between rapid or usual gait speeds, as integrative measures of motor function, and cerebral myelin content. In 118 individuals (age 22-94 years) free of neurodegenerative diseases or cognitive impairment, myelin content was assessed as the myelin water fraction, a direct magnetic resonance imaging measure of myelin content, and longitudinal and transverse relaxation rates (R1 and R2), which are sensitive magnetic resonance imaging measures of myelin content. Our results indicate that participants with lower usual or rapid gait speed exhibited lower values of myelin water fraction and R1 in the main brainstem regions, which were more evident and statistically significant in the midbrain. In contrast, we found no significant associations between gait speeds and R2, an expected result because various physiological factors confound R2. These original findings provide evidence that the level of brainstem myelination may affect gait performance among cognitively unimpaired adults who are free from any clinically detectable neurodegenerative diseases. Further studies are needed to understand the longitudinal changes in brainstem myelination with aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":"2214-2221"},"PeriodicalIF":4.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rita Peila, Xiaonan Xue, Aladdin H Shadyab, Jean Wactawski-Wende, Mark A Espeland, Linda G Snetselaar, Nazmus Saquib, Farha Ikramuddin, JoAnn E Manson, Robert B Wallace, Thomas E Rohan
Background: Multimorbidity, defined as the presence of 2 or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity (PA), sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and risk of multimorbidity are not well understood.
Objectives: We investigated the association between the healthy lifestyle index (HLI), generated by combining indicators of diet quality, smoking, alcohol, PA, sleep amount, and BMI, and risk of multimorbidity, a composite outcome that included cardiovascular disease (CVD), diabetes, cancer, and fracture.
Methods: We studied 62 037 postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative, with no reported history of CVD, diabetes, cancer, or fracture at baseline. Lifestyle characteristics measured at baseline were categorized and a score (0-4) was assigned to each category. The combined HLI (0-24) was grouped into quintiles, with higher quintiles indicating a healthier lifestyle. Multivariable adjusted estimates of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of developing multimorbidity were obtained using Cox proportional hazard models.
Results: Over an average follow-up period of 16.3 years, 5 656 women developed multimorbidity. There was an inverse association between the HLI levels and risk of multimorbidity (compared to the HLI_1st quintile: HR_2nd quintile = 0.81 95% CI 0.74-0.83, HR_3rd quintile = 0.77 95% CI 0.71-0.83, HR_4th quintile = 0.70 95% CI 0.64-0.76, and HR_5th quintile = 0.60 95% CI 0.54-0.66; p trend < .001). Similar associations were observed after stratification by age or BMI categories.
Conclusions: Among postmenopausal women, higher levels of the HLI were associated with a reduced risk of developing multimorbidity.
背景:多重疾病,定义为存在两种或两种以上的慢性健康状况,在老年人中越来越普遍。生活方式特征,如饮食质量、吸烟状况、饮酒、身体活动(PA)、睡眠时间和身体脂肪(以体重指数(BMI)或腰围评估)与多病风险的组合尚未得到很好的理解。目的:我们研究了健康生活方式指数(HLI)与多病风险(包括心血管疾病(CVD)、糖尿病、癌症和骨折)之间的关系,HLI是由饮食质量、吸烟、饮酒、PA、睡眠时间和BMI等综合指标产生的。方法:我们研究了62 037名年龄在50-79岁的绝经后妇女,她们在基线时没有心血管疾病、糖尿病、癌症或骨折史。在基线测量的生活方式特征进行分类,并为每个类别分配一个分数(0-4)。综合健康指数(0-24)分为五分位数,五分位数越高表明生活方式越健康。使用Cox比例风险模型获得多变量调整后的多发病风险比(hr)和95%置信区间(95% ci)。结果:在平均16.3年的随访期间,5656名女性出现了多病。HLI水平与多病风险呈负相关(与hli1五分位数相比:hr2五分位数= 0.81 95% CI 0.74-0.83, hr3五分位数= 0.77 95% CI 0.71-0.83, hr4五分位数= 0.70 95% CI 0.64-0.76, hr5五分位数= 0.60 95% CI 0.54-0.66;结论:在绝经后妇女中,较高水平的HLI与发生多种疾病的风险降低相关。
{"title":"Association Between the Healthy Lifestyle Index and Risk of Multimorbidity in the Women's Health Initiative.","authors":"Rita Peila, Xiaonan Xue, Aladdin H Shadyab, Jean Wactawski-Wende, Mark A Espeland, Linda G Snetselaar, Nazmus Saquib, Farha Ikramuddin, JoAnn E Manson, Robert B Wallace, Thomas E Rohan","doi":"10.1093/gerona/glad170","DOIUrl":"10.1093/gerona/glad170","url":null,"abstract":"<p><strong>Background: </strong>Multimorbidity, defined as the presence of 2 or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity (PA), sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and risk of multimorbidity are not well understood.</p><p><strong>Objectives: </strong>We investigated the association between the healthy lifestyle index (HLI), generated by combining indicators of diet quality, smoking, alcohol, PA, sleep amount, and BMI, and risk of multimorbidity, a composite outcome that included cardiovascular disease (CVD), diabetes, cancer, and fracture.</p><p><strong>Methods: </strong>We studied 62 037 postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative, with no reported history of CVD, diabetes, cancer, or fracture at baseline. Lifestyle characteristics measured at baseline were categorized and a score (0-4) was assigned to each category. The combined HLI (0-24) was grouped into quintiles, with higher quintiles indicating a healthier lifestyle. Multivariable adjusted estimates of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of developing multimorbidity were obtained using Cox proportional hazard models.</p><p><strong>Results: </strong>Over an average follow-up period of 16.3 years, 5 656 women developed multimorbidity. There was an inverse association between the HLI levels and risk of multimorbidity (compared to the HLI_1st quintile: HR_2nd quintile = 0.81 95% CI 0.74-0.83, HR_3rd quintile = 0.77 95% CI 0.71-0.83, HR_4th quintile = 0.70 95% CI 0.64-0.76, and HR_5th quintile = 0.60 95% CI 0.54-0.66; p trend < .001). Similar associations were observed after stratification by age or BMI categories.</p><p><strong>Conclusions: </strong>Among postmenopausal women, higher levels of the HLI were associated with a reduced risk of developing multimorbidity.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":"2282-2293"},"PeriodicalIF":4.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}