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Near-Lifespan Tracking of Cerebral Microvascular Degeneration in Aging to Alzheimer’s Continuum 老年至阿尔茨海默病连续体中大脑微血管变性的近寿命跟踪
Pub Date : 2022-03-29 DOI: 10.20900/agmr20220003
Jonghwan Lee
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting millions of people worldwide and is currently incurable. As the population ages, AD and related dementia are becoming the biggest epidemic in medical history: the number of people aged 65 and older with AD is projected to increase between two- and three-fold by 2050. Imaging and biomarker studies suggest that the pathophysiological processes of AD begin more than a decade before the diagnosis of dementia, opening the possibility of early, preemptive prediction. For accurate prediction, it is important although challenging to fully understand how multiple etiologies and age-related prodromal processes contribute to the onset of Alzheimer’s continuum, across a long period comparable to the lifespan. Addressing this challenge was one of the overarching transformative concepts at the 2015 AD Research Summit, “to develop new programs on systems biology and integrative physiology to gain a deeper understanding of the complex biology of the disease.” Among other factors, cerebral microvascular degeneration (CMD) may play a key role in the onset and development of Alzheimer’s continuum, potentially prior to, along with, or independently of the beta-amyloid (Aβ) accumulation. Despite its importance for early detection and as a therapeutic target for early intervention, it is unknown whether CMD is a causal factor for AD pathogenesis or an early consequence of multifactorial conditions that lead to AD at a later stage. Here, this Viewpoint suggests that we should fill two critical knowledge gaps: (1) Temporal relationships between various CMDs and other key factors before/during/after the onset of Alzheimer’s continuum have not been established; (2) Little integrative study down to the capillary vessel level has been conducted on how individual defects in various microvascular structural and flow properties distinctly correlate with and/or contribute to neuronal degeneration. As the first step toward filling these gaps, I propose utilizing recent advances in microscopic imaging and image analysis techniques to longitudinally track a comprehensive set of CMDs over the lifespan in model animals, along with Aβ, tau, neuronal degeneration, and cognitive impairment when possible.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,影响着全世界数百万人,目前无法治愈。随着人口老龄化,阿尔茨海默病和相关的痴呆症正在成为医学史上最大的流行病:到2050年,65岁及以上的阿尔茨海默病患者人数预计将增加两到三倍。影像学和生物标志物研究表明,阿尔茨海默病的病理生理过程在痴呆症诊断前十多年就开始了,这为早期、先发制人的预测提供了可能。为了准确预测,充分了解多种病因和与年龄相关的前驱过程如何导致阿尔茨海默病的连续发作,这是很重要的,尽管具有挑战性,跨越与生命周期相当的长时间。应对这一挑战是2015年阿尔茨海默病研究峰会的首要变革概念之一,“开发系统生物学和综合生理学的新项目,以更深入地了解疾病的复杂生物学。”在其他因素中,脑微血管变性(CMD)可能在阿尔茨海默病连续体的发生和发展中发挥关键作用,可能先于,伴随或独立于β -淀粉样蛋白(a β)积累。尽管CMD对于早期发现和作为早期干预的治疗靶点具有重要意义,但尚不清楚它是否是AD发病的一个因果因素,还是多因素疾病在后期导致AD的早期后果。在此,这一观点建议我们应该填补两个关键的知识空白:(1)各种CMDs与其他关键因素在阿尔茨海默病连续体发病前/期间/之后的时间关系尚未建立;(2)关于各种微血管结构和血流特性的个体缺陷如何与神经元变性明显相关和/或促成神经元变性的综合研究很少深入到毛细血管水平。作为填补这些空白的第一步,我建议利用显微镜成像和图像分析技术的最新进展,在模型动物的整个生命周期中纵向跟踪一套全面的cmd,以及a β, tau,神经元变性和认知障碍。
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引用次数: 1
Linoleic Acid Intake and Physical Function: Pilot Results from the Health ABC Energy Expenditure Sub-Study 亚油酸摄入和身体功能:健康ABC能量消耗子研究的试点结果
Pub Date : 2022-02-16 DOI: 10.20900/agmr20220001
M. Belury, B. Clark, R. McGrath, P. Cawthon
Background: Dietary fat quality is important for health and physical functioning in older adults. Linoleic acid is a dietary polyunsaturated fatty acid that is necessary for optimal inner-mitochondrial membrane function. However, limited evidence exists for examining the role of linoleic acid intake on indices of mobility and physical function. In this pilot study, we sought to examine the associations between linoleic acid intake and physical functioning in older adults. Methods: This secondary analysis of data from the Health, Aging, and Body Composition energy expenditure sub-study was conducted for our investigation. Ability to complete physical tasks such as climbing a flight of stairs, walking a quarter mile, and lifting 10 lbs. was self-reported. Daily linoleic acid intake was estimated from a food frequency questionnaire. Persons with daily linoleic acid intake below approximately 85% of Adequate Intake were considered as having low linoleic acid intake. Covariate-adjusted logistic models were used for the analyses. Results: The final analytical sample included 317 participants aged 74.4 ± 2.8 years who consumed 18.9 ± 11.4 g/day of linoleic acid, with 78 (24.6%) participants having low daily linoleic acid intake. Persons with low daily linoleic acid intake had 2.58 (95% confidence interval: 1.27–5.24) greater odds for a limitation in climbing stairs. Conclusions: Our pilot investigation found that low daily linoleic acid intake could be associated with physical function in older adults. Dietitians working with older patients may want to consider the importance of daily linoleic acid intake for health and certain physical function tasks.
背景:膳食脂肪质量对老年人的健康和身体功能很重要。亚油酸是一种膳食多不饱和脂肪酸,是线粒体内膜最佳功能所必需的。然而,研究亚油酸摄入量对运动能力和身体功能指标的作用的证据有限。在这项初步研究中,我们试图研究亚油酸摄入量与老年人身体功能之间的关系。方法:对健康、衰老和身体组成能量消耗子研究的数据进行二次分析。能够完成体力活动,如爬一段楼梯,走四分之一英里,举起10磅。是自我报告。每日亚油酸摄入量通过食物频率问卷进行估算。每日亚油酸摄入量低于充足摄入量约85%的人被视为亚油酸摄入量低。采用协变量校正logistic模型进行分析。结果:最终的分析样本包括317名年龄为74.4±2.8岁的参与者,他们每天摄入18.9±11.4 g亚油酸,其中78名(24.6%)参与者的每日亚油酸摄入量较低。每日亚油酸摄入量低的人有2.58(95%可信区间:1.27-5.24)高的几率限制爬楼梯。结论:我们的初步调查发现,每日亚油酸摄入量低可能与老年人的身体功能有关。与老年患者一起工作的营养师可能需要考虑每日亚油酸摄入量对健康和某些身体功能任务的重要性。
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引用次数: 3
The Predictive Validity and Clinical Application of Stopping Elderly Accidents, Deaths & Injuries (STEADI) for Fall Risk Screening. 停止老年人意外、死亡和伤害(STEADI)在跌倒风险筛查中的预测有效性和临床应用。
Pub Date : 2022-01-01 Epub Date: 2022-09-30 DOI: 10.20900/agmr20220008
Chia-Cheng Lin, Stacey Meardon, Kevin O'Brien

Fall prevention is critical for older adults. Stopping Elderly Accidents, Deaths, and Injuries (STEADI) is a fall prevention initiative, promoted by the Center for Disease Control (CDC). The purpose of this review aims to discuss the predictive validity, improve the predictive validity of STEADI, and apply STEADI in clinical settings.

预防跌倒对老年人至关重要。停止老年人事故、死亡和伤害(STEADI)是一项预防跌倒的倡议,由疾病控制中心(CDC)推动。本综述旨在探讨STEADI的预测效度,提高其预测效度,并将其应用于临床。
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引用次数: 0
Effects of Low-Volume High-Intensity Interval Training Compared to Moderate-Intensity Continuous Training on Inflammatory Profile in Women with Type 2 Diabetes 与中强度连续训练相比,低量高强度间歇训练对2型糖尿病女性炎症的影响
Pub Date : 2022-01-01 DOI: 10.20900/agmr20220007
A. Marcotte-Chénard, Renaud Tremblay, M. Mony, D. Tremblay, P. Boulay, M. Brochu, J. Morais, I. Dionne, M. Langlois, W. Mampuya, D. Tessier, E. Riesco
Background : The objective was to compare the effects of low-volume high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on the inflammatory profile in older women with type 2 diabetes (T2D). Methods : Thirty older physically inactive women (68 ± 5 years) with T2D were randomized in two groups: HIIT (75 min/week with 10 min/session at high intensity) or MICT (150 min/week). Inflammatory profile (IL-6, IL-10, IL-15, TNF- α , and MCP-1; Luminex), body composition (iDXA), and cardiometabolic profile (A1c, glucose, insulin, lipids) were measured in fasting state, before and after the 3-month intervention in 27 participants. Results : While fasting levels of cytokines remained unchanged in the MICT group ( p ≥ 0.18), circulating MCP-1 levels increased (from 160.9 [IQR: 133.5–230.2] to 187.88 [155.3–237.3]) in the HIIT group ( p = 0.023). Linear regression revealed that changes in MCP-1 concentrations were positively associated with changes in A1c ( adjusted R 2 = 0.203; p = 0.018). Conclusions : The results of this study suggest that 12 weeks of either low-volume HIIT or MICT do not improve inflammatory markers in older unfit women with T2D. The correlation between changes in A1c and MCP-1 levels support the role of hyperglycemia in low-grade inflammation.
背景:目的是比较低容量高强度间歇训练(HIIT)和中等强度连续训练(MICT)对老年2型糖尿病(T2D)女性炎症的影响。方法:30名老年无运动的T2D女性(68±5岁)随机分为两组:HIIT(75分钟/周,高强度10分钟/次)和MICT(150分钟/周)。炎症谱(IL-6、IL-10、IL-15、TNF- α和MCP-1;在干预3个月前后的空腹状态下测量27名参与者的Luminex、体成分(iDXA)和心脏代谢谱(A1c、葡萄糖、胰岛素、血脂)。结果:MICT组空腹细胞因子水平保持不变(p≥0.18),HIIT组循环MCP-1水平升高(从160.9 [IQR: 133.5-230.2]增加到187.88 [155.3-237.3])(p = 0.023)。线性回归显示MCP-1浓度的变化与A1c的变化呈正相关(校正r2 = 0.203;P = 0.018)。结论:本研究的结果表明,12周的低容量HIIT或MICT并不能改善老年不适t2dm女性的炎症标志物。A1c和MCP-1水平变化之间的相关性支持高血糖在低度炎症中的作用。
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引用次数: 0
Aging Diminishes Mucociliary Clearance of the Lung. 衰老减少肺纤毛粘液清除。
Pub Date : 2022-01-01 Epub Date: 2022-06-27 DOI: 10.20900/agmr20220005
Kristina L Bailey

Healthy aging leads to a decrease in mucociliary clearance of the lung. Mucociliary clearance is an essential innate immune defense to protect against inhaled particles and microbes. Mucociliary clearance can be affected by changes in cilia function as well as mucus quantity and qualities. With aging, cilia beat frequency slows and there are changes to the characteristics of mucus. These decreases in mucociliary clearance may lead to lung infection such as pneumonia or airway diseases such as bronchiectasis or Chronic Obstructive Pulmonary Diseases.

健康的衰老导致肺部纤毛黏液清除率的降低。纤毛粘液清除是一种必要的先天免疫防御,以防止吸入颗粒和微生物。纤毛粘液清除可受纤毛功能变化以及粘液数量和质量的影响。随着年龄的增长,纤毛的跳动频率减慢,粘液的特征也发生了变化。纤毛黏液清除的减少可能导致肺部感染,如肺炎或气道疾病,如支气管扩张或慢性阻塞性肺疾病。
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引用次数: 5
Aging of Skeletal Stem Cells. 骨骼干细胞的衰老。
Pub Date : 2022-01-01 Epub Date: 2022-06-30 DOI: 10.20900/agmr20220006
M Gohazrua K Butler, Thomas H Ambrosi, Matthew P Murphy, Charles K F Chan

The skeletal system is generated and maintained by its progenitors, skeletal stem cells (SSCs), across the duration of life. Gradual changes associated with aging result in significant differences in functionality of SSCs. Declines in bone and cartilage production, increase of bone marrow adipose tissue, compositional changes of cellular microenvironments, and subsequent deterioration of external and internal structures culminate in the aged and weakened skeleton. The features and mechanisms of skeletal aging, and of its stem and progenitor cells in particular, are topics of recent investigation. The discovery of functionally homogeneous SSC populations with a defined cell surface phenotype has allowed for closer inspection of aging in terms of its effects on transcriptional regulation, cell function, and identity. Here, we review the aspects of SSC aging on both micro- and macroscopic levels. Up-to-date knowledge of SSC biology and aging is presented, and directions for future research and potential therapies are discussed. The realm of SSC-mediated bone aging remains an important component of global health and a necessary facet in our understanding of human aging.

骨骼系统是由其祖细胞--骨骼干细胞(SSCs)在整个生命过程中生成和维持的。随着年龄的增长,骨骼干细胞的功能会逐渐发生显著变化。骨骼和软骨生成的减少、骨髓脂肪组织的增加、细胞微环境成分的变化以及随后外部和内部结构的恶化,最终导致骨骼老化和衰弱。骨骼衰老,特别是骨骼干细胞和祖细胞衰老的特征和机制是近期研究的主题。具有明确细胞表面表型的功能均一的造血干细胞群的发现,使我们能够从其对转录调控、细胞功能和特性的影响方面对衰老进行更深入的研究。在此,我们从微观和宏观两个层面回顾了造血干细胞衰老的各个方面。本文介绍了有关造血干细胞生物学和衰老的最新知识,并讨论了未来的研究方向和潜在疗法。造血干细胞介导的骨老化领域仍然是全球健康的一个重要组成部分,也是我们了解人类衰老的一个必要方面。
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引用次数: 0
Aging, Cutaneous Burn Injury and Multi-Organ Complications: The Role of the Gut. 衰老、皮肤烧伤和多器官并发症:肠道的作用
Pub Date : 2022-01-01 Epub Date: 2022-06-28 DOI: 10.20900/agmr20220004
Rachel H McMahan, Devin M Boe, Travis M Walrath, Juan-Pablo Idrovo, Elizabeth J Kovacs

Advanced age escalates post-burn complications and older burn patients, and even those with relatively minor burns, have worse clinical outcomes after injury. While the mechanism(s) responsible for the compounding effects of age and burn injury have not been defined, in this viewpoint, we highlight the emerging data suggesting that age-mediated impairment of gut barrier integrity and dysbiosis of the fecal microbiome in older subjects may play a role in the heightened multi-organ responses seen in older patients. Studies aimed at exploring the contribution of intestinal dysfunction in age-related exacerbations of post-burn inflammatory responses could highlight novel therapeutic interventions that can be used to treat victims of burns and other traumatic injuries.

高龄会增加烧伤后的并发症,年龄较大的烧伤患者,甚至是烧伤程度相对较轻的患者,伤后的临床预后会更差。虽然造成年龄和烧伤复合效应的机制尚未确定,但我们在本文中强调了新出现的数据,这些数据表明,年龄介导的老年受试者肠道屏障完整性受损和粪便微生物群失调可能是老年患者多器官反应加重的原因之一。旨在探索肠道功能障碍在与年龄相关的烧伤后炎症反应加重中的作用的研究,可以突出可用于治疗烧伤和其他创伤受害者的新型治疗干预措施。
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引用次数: 0
Loneliness and Neurocognitive Aging. 孤独和神经认知老化。
Pub Date : 2021-01-01 Epub Date: 2021-03-29 DOI: 10.20900/agmr20210009
R Nathan Spreng, Danilo Bzdok

Loneliness imposes significant risks to physical, mental and brain health in older adulthood. With the social distancing regimes implemented during the COVID-19 pandemic, there is even greater urgency to understand the human health costs of social isolation. In this viewpoint we describe how the experience of loneliness may alter the structure and function of the human brain, and how these discoveries may guide public health policy to reduce the burden of loneliness in later life.

孤独对老年人的身体、精神和大脑健康构成重大风险。随着2019冠状病毒病大流行期间实施的社会距离制度,了解社会隔离对人类健康造成的代价变得更加紧迫。在这一观点中,我们描述了孤独的经历如何改变人类大脑的结构和功能,以及这些发现如何指导公共卫生政策,以减轻晚年生活中孤独的负担。
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引用次数: 5
Strategies to Prevent Serious Fall Injuries: A Commentary on Bhasin et al. A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries. N Engl J Med. 2020;383(2):129-140. 预防严重跌倒伤害的策略:对Bhasin等人的评论。预防严重跌倒损伤的多因素随机试验中华医学杂志,2020;32(2):129-140。
Pub Date : 2021-01-01 Epub Date: 2020-11-14 DOI: 10.20900/agmr20210002
Brian C Clark, W David Arnold

Every second of every day, an older adult suffers a fall in the United States (>30 million older adults fall each year). More than 20% of these falls cause serious injury (e.g., broken bones, head injury) and result in 800,000 hospitalizations and 30,000 deaths annually. Bhasin and colleagues recently reported results from a pragmatic, cluster-randomized trial designed to evaluate the effectiveness of a multifactorial intervention to prevent fall injuries. The intervention did not result in a significantly lower rate of a first adjudicated serious fall injury among older adults at increased risk for fall injuries as compared with enhanced usual care. In this commentary we briefly review and highlight these recent findings. Additionally, we argue that the findings should not be discounted just because of the lack of statistical significance. The approximately 10% reduction compared to enhanced usual care is, arguably, meaningful at both the individual and public health level, especially when one considers that the control group had better outcomes than expected based on prior work. Moreover, we encourage future research as well as practitioners to give strong consideration to the nuances of the exercise interventions for reducing falls and fall-related injuries particularly as it relates to exercise programming specifics, namely intensity and volume, to enhance neuromuscular function and also to neurorehabilitation approaches to enhance motor function (e.g., balance, motor planning, and coordination).

在美国,每天每秒钟都有一名老年人跌倒(每年有超过3000万老年人跌倒)。其中20%以上的摔伤造成严重伤害(例如骨折、头部受伤),每年造成80万人住院,3万人死亡。Bhasin和他的同事最近报道了一项实用的集群随机试验的结果,该试验旨在评估多因素干预预防跌倒损伤的有效性。与增强的常规护理相比,干预并没有导致跌倒损伤风险增加的老年人首次确诊严重跌倒损伤的发生率显著降低。在这篇评论中,我们简要回顾和强调这些最近的发现。此外,我们认为研究结果不应该仅仅因为缺乏统计显著性而打折扣。与增强的常规护理相比,大约减少了10%,可以说,在个人和公共卫生水平上都是有意义的,特别是当人们考虑到对照组的结果比基于先前工作的预期要好时。此外,我们鼓励未来的研究以及从业者对运动干预的细微差别给予强烈的考虑,以减少跌倒和跌倒相关的伤害,特别是当它涉及到运动计划的细节,即强度和体积,以增强神经肌肉功能,以及神经康复方法以增强运动功能(例如,平衡,运动计划和协调)。
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引用次数: 6
Oral Conditions, Oral Health Related Quality of Life and Cognitive Function: Preliminary Results from the Health and Retirement Study 口腔状况、口腔健康相关的生活质量和认知功能:健康与退休研究的初步结果
Pub Date : 2021-01-01 DOI: 10.20900/agmr20210020
P. Joshi, Laura B. Kaufman, H. Cabral
Background: Growing evidence suggests that cognitive functioning is influenced by oral health status. This study examines the association between the status or condition of the mouth as measured by self-report (OH), oral health related quality of life (OHRQoL) and dental care utilization on cognitive function. Design: Population‐based cross‐sectional study. Setting: United States Health and Retirement Study (2018). Participants: Community‐dwelling adults above 50 years of age (N = 1268; Mean age (SD) 67.14 ± 10.54 years). Measurements: Self-reported condition of mouth and teeth, number of teeth and denture use were used to determine the OH. OHRQoL was assessed as a composite score using self-reported pain or distress due to gums or teeth, difficulty to relax, avoiding eating certain foods, or socializing due to oral health issues. Validated cognitive score cut-offs were used: (i) (≥12) representing normal cognition (ii) (6–11) “cognitive impairment, not demented” (CIND), and (iii) (<6) dementia. Results: We found that participants with worse OHRQoL had 0.15 units lower global cognitive scores (β = −0.15, SE = 0.03, p = < 0.0001). Compared to those with dementia, participants in normal and CIND categories had greater odds of better OH (ORNormal = 1.76, (95%CI: 1.09–2.84); ORCIND = 2.86, (95%CI: 1.60–5.09)). Furthermore, participants in the CIND category had greater odds of using dentures compared to participants with dementia (ORCIND = 2.71, (95%CI: 1.49–4.93)). We did not find any statistically significant association between tooth loss or dental utilization and dementia. Open Access Received: 05 March 2020 Accepted: 22 December 2021 Published: 29 December 2021 Copyright © 2021 by the author(s). Licensee Hapres, London, United Kingdom. This is an open access article distributed under the terms and conditions of Creative Commons Attribution 4.0 International License. Advances in Geriatric Medicine and Research 2 of 12 Conclusions: This study provides valuable preliminary insights into the potential association between OH and OHRQoL and cognitive function. If further validated, this method may allow dental and cognitive triage for follow-up assessments in community dwelling adults who may have limited access to care.
背景:越来越多的证据表明,认知功能受口腔健康状况的影响。本研究探讨口腔自我报告状态(OH)、口腔健康相关生活质量(OHRQoL)和牙科保健利用对认知功能的影响。设计:基于人群的横断面研究。背景:美国健康与退休研究(2018)。参与者:50岁以上居住在社区的成年人(N = 1268;平均年龄(SD) 67.14±10.54岁。测量方法:采用自述口腔和牙齿状况、牙齿数量和假牙使用情况来测定OH。OHRQoL被评估为一个综合评分,使用自我报告的牙龈或牙齿疼痛或痛苦、难以放松、避免吃某些食物或因口腔健康问题而社交。使用经过验证的认知评分截断值:(i)(≥12)代表正常认知;(ii)(6 - 11)“认知障碍,非痴呆”(CIND); (iii)(<6)痴呆。结果:我们发现OHRQoL较差的参与者整体认知评分降低0.15个单位(β = - 0.15, SE = 0.03, p = < 0.0001)。与痴呆症患者相比,正常和CIND类别的参与者有更大的机会获得更好的OH (ORNormal = 1.76, (95%CI: 1.09-2.84);orci = 2.86, (95%ci: 1.60-5.09)。此外,与痴呆患者相比,CIND患者使用假牙的几率更大(ORCIND = 2.71, 95%CI: 1.49-4.93)。我们没有发现牙齿脱落或牙齿使用与痴呆之间有统计学意义的关联。开放获取接收日期:2020年3月05日接收日期:2021年12月22日发布日期:2021年12月29日版权所有©作者:2021。被许可方Hapres,伦敦,英国。这是一篇在知识共享署名4.0国际许可条款和条件下发布的开放获取文章。结论:本研究为OH和OHRQoL与认知功能之间的潜在关联提供了有价值的初步见解。如果进一步验证,该方法可能允许牙科和认知分诊,对社区居住的成年人进行随访评估,这些成年人可能无法获得护理。
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引用次数: 0
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Advances in geriatric medicine and research
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