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Highlights of the EuGMS congress 2024 2024 年欧洲地质调查局大会的亮点。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.lanhl.2024.100657
Philippa Harris
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引用次数: 0
Early integration of palliative care versus standard cardiac care for patients with heart failure (EPCHF): a multicentre, parallel, two-arm, open-label, randomised controlled trial 心力衰竭患者早期整合姑息关怀与标准心脏护理(EPCHF):一项多中心、平行、双臂、开放标签、随机对照试验。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lanhl.2024.08.006
Mahmoud Balata MD , Prof Lukas Radbruch MD , Michaela Hesse MD , Prof Ralf Westenfeld MD , Martin Neukirchen MD , Prof Roman Pfister MD , Yann-Nicolas Batzler MD , Can Öztürk MD , Refik Kavsur MD , Vedat Tiyerili MD , Prof Birgitta Weltermann MD , Robert Pölsler MD , Prof Thomas Standl MD , Prof Georg Nickenig MD , Prof Marc Ulrich Becher MD , Heart Failure Network Rhineland

Background

Heart failure is a substantial global health concern that severely affects patients' quality of life. We aimed to compare the effects of early integration of palliative care (EIPC) and standard cardiac care on health status and mood of patients with non-terminal heart failure.

Methods

EPCHF was a multicentre, parallel, two-arm, open-label, randomised controlled trial carried out at University Hospital Bonn and University Hospital Düsseldorf in Germany. Eligible patients (aged 18 years or older) had heart failure, with New York Heart Association class II or more and NT-proBNP concentrations greater than or equal to 400 pg/mL. Patients were randomly assigned (1:1) to receive EIPC with standard cardiac care or standard cardiac care alone. Randomisation was computer-generated with allocation concealment, variable block sizes, and stratification by investigational site. The primary endpoints were health status and mood, measured every 3 months over 12 months using the Functional Assessment of Chronic Illness Therapy–Palliative Care (FACIT–PAL) and the Kansas City Cardiomyopathy Questionnaire (KCCQ), analysed by intention to treat. This trial is registered with DRKS.de, DRKS00013922.

Findings

Between May 21, 2019, and Nov 15, 2021, 843 patients were assessed for eligibility, 205 of whom were enrolled (100 assigned to EIPC and 105 assigned to standard cardiac care). 143 (70%) patients were male and 62 (30%) were female. Over 12 months, both groups significantly improved in FACIT–PAL and KCCQ Overall Summary Score (OSS) with no significant differences between the groups (FACIT–PAL adjusted mean difference 0·98 points [95% CI –1·28 to 3·23]; p=0·40; KCCQ-OSS adjusted mean difference –2·06 points [–7·89 to 3·78]; p=0·49). Nine (9%) patients in the EIPC group and seven (7%) patients in the standard cardiac care group died from any cause, with no significant differences in time to death between the two groups (hazard ratio [HR] 1·32 [95% CI 0·49 to 3·54]; p=0·58). 22 (22%) patients in the EIPC group and 21 (21%) patients in the standard cardiac care group were hospitalised at least once due to heart failure, with no significant differences in time to heart-failure-related hospitalisation between the two groups (HR 1·09 [0·61 to 1·98]; p=0·77). 70 (70%) patients in the EIPC group and 62 (59%) in the standard cardiac care group had any adverse events (p=0·10).

Interpretation

In this open-label, randomised clinical trial, standard cardiac care, featuring guideline-directed optimisation of medical therapy and regular 3-monthly follow-ups was found to be as effective as when combined with EIPC in improving health status and mood in patients with non-terminal heart failure. Future clinical practices should consider EIPC based on individual patient needs.

Funding

Federal Ministry of Education and Research.
背景:心力衰竭是一个严重影响患者生活质量的全球性健康问题。我们旨在比较早期整合姑息治疗(EIPC)和标准心脏治疗对非终末期心力衰竭患者健康状况和情绪的影响:EPCHF是一项多中心、平行、双臂、开放标签、随机对照试验,在德国波恩大学医院和杜塞尔多夫大学医院进行。符合条件的患者(18 岁或以上)均患有心力衰竭,纽约心脏协会分级为 II 级或以上,NT-proBNP 浓度大于或等于 400 pg/mL。患者被随机分配(1:1)接受 EIPC 和标准心脏治疗,或仅接受标准心脏治疗。随机分配由计算机生成,采用分配隐藏、可变区块大小和按研究地点分层的方式。主要终点是健康状况和情绪,在12个月内每3个月使用慢性疾病治疗-姑息治疗功能评估(FACIT-PAL)和堪萨斯城心肌病问卷(KCCQ)进行测量,并按意向治疗进行分析。该试验已在DRKS.de注册,编号为DRKS00013922.Findings:2019年5月21日至2021年11月15日期间,843名患者接受了资格评估,其中205名患者入选(100名被分配至EIPC,105名被分配至标准心脏护理)。143名患者(70%)为男性,62名患者(30%)为女性。在12个月内,两组患者的FACIT-PAL和KCCQ综合评分(OSS)均有明显改善,组间无明显差异(FACIT-PAL调整后平均差异为0-98分[95% CI -1-28 to 3-23];P=0-40;KCCQ-OSS调整后平均差异为-2-06分[-7-89 to 3-78];P=0-49)。EIPC组有9名(9%)患者因任何原因死亡,标准心脏护理组有7名(7%)患者因任何原因死亡,两组患者的死亡时间无显著差异(危险比[HR] 1-32 [95% CI 0-49 to 3-54]; p=0-58)。EIPC组22(22%)名患者和标准心脏护理组21(21%)名患者因心衰至少住院一次,两组患者因心衰住院的时间无显著差异(HR 1-09 [0-61 to 1-98]; p=0-77)。EIPC组有70名(70%)患者出现不良事件,标准心脏护理组有62名(59%)患者出现不良事件(P=0-10):在这项开放标签、随机临床试验中发现,标准心脏治疗,包括以指南为指导的优化药物治疗和3个月定期随访,在改善非终末期心力衰竭患者的健康状况和情绪方面与EIPC联合治疗同样有效。未来的临床实践应根据患者的个体需求考虑EIPC:联邦教育与研究部。
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引用次数: 0
Use of biomarkers in the diagnosis of Alzheimer’s disease in adults with intellectual disability 使用生物标志物诊断智障成人阿尔茨海默病。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lanhl.2024.100639
Aoife McFeely MB , Antoinette O’Connor MB PhD , Prof Sean P Kennelly MB PhD
People with intellectual disability are a vulnerable cohort who face challenges accessing health care. Compared with the general population, people with intellectual disability have an elevated risk of developing dementia, which often presents at a younger age and with atypical symptoms. The lifelong cognitive and functional difficulties faced by people with intellectual disability further complicate the diagnostic process. Specialised intellectual disability memory services and evaluation using reliable biomarkers of neurodegeneration are needed to improve diagnostic and prognostic certainty in this group. Inadequate specialist services and paucity of research on biomarkers in this population hinders progress and impedes the delivery of adequate health care. Although cerebrospinal fluid-based biomarkers and radiological biomarkers are used routinely in the evaluation of Alzheimer’s disease in the general population, biological variation within the clinically heterogenous group of people with intellectual disability could affect the clinical utility of existing biomarkers. As disease-modifying therapies become available for the treatment of early Alzheimer’s disease, and hopefully other neurodegenerative conditions in the future, biomarkers will serve as gatekeepers to establish the eligibility for such therapies. Inadequate representation of adults with intellectual disability in biomarker research will result in their exclusion from treatment with disease-modifying therapies, thus perpetuating the inequity in health care that is already faced by this group. The aim of this Series paper is to summarise current evidence on the application of biomarkers for Alzheimer’s disease in a population with intellectual disability (that is not attributable to Down syndrome) and suspected cognitive decline.
智障人士是弱势群体,他们在获得医疗保健服务方面面临挑战。与普通人群相比,智障人士罹患痴呆症的风险更高,而且痴呆症的发病年龄往往更小,症状也不典型。智障人士终生面临的认知和功能障碍使诊断过程更加复杂。需要提供专门的智障记忆服务,并使用可靠的神经变性生物标志物进行评估,以提高该群体诊断和预后的确定性。专科服务的不足和对这一人群生物标志物研究的匮乏阻碍了进展,并妨碍了提供适当的医疗保健服务。虽然基于脑脊液的生物标志物和放射学生物标志物已被常规用于评估普通人群中的阿尔茨海默病,但在临床上具有异质性的智障人士群体中的生物变异可能会影响现有生物标志物的临床效用。随着可用于治疗早期阿尔茨海默病的疾病改变疗法的出现,以及希望将来能用于治疗其他神经退行性疾病,生物标志物将成为确定是否有资格接受此类疗法的把关人。智障成人在生物标志物研究中的代表性不足,将导致他们被排除在疾病改变疗法的治疗范围之外,从而使这一群体已经面临的医疗保健不公平现象永久化。本系列论文旨在总结目前在智障(非唐氏综合症所致)和疑似认知能力下降人群中应用阿尔茨海默病生物标志物的证据。
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引用次数: 0
Mental health deserves attention at all ages 所有年龄段的人都应关注心理健康。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lanhl.2024.100650
The Lancet Healthy Longevity
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引用次数: 0
Clinical effectiveness of DREAMS START (Dementia Related Manual for Sleep; Strategies for Relatives) versus usual care for people with dementia and their carers: a single-masked, phase 3, parallel-arm, superiority randomised controlled trial DREAMS START(痴呆症相关睡眠手册;亲属策略)与痴呆症患者及其照护者常规照护的临床效果:单掩蔽、第 3 阶段、平行臂、优越性随机对照试验。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lanhl.2024.08.004
Prof Penny Rapaport PhD , Sarah Amador PhD , Mariam O Adeleke PhD , Prof Julie A Barber PhD , Prof Sube Banerjee MD , Prof Georgina Charlesworth PhD , Chris Clarke DClinPsy , Prof Colin A Espie DSc , Lina Gonzalez MSc , Rossana Horsley GradCert , Prof Rachael Hunter MSc , Prof Simon D Kyle PhD , Monica Manela BM , Malgorzata Raczek PhD , Prof Zuzana Walker MD , Lucy Webster PhD , Hang Yuan PhD , Prof Gill Livingston MD

Background

Sleep disturbances are common and distressing for people with dementia and their families. Non-pharmacological interventions should be first-line management, avoiding harmful pharmacological side-effects, but there is none with known effectiveness. We aimed to establish whether DREAMS START, a multicomponent intervention, reduced sleep disturbance in people with dementia living at home compared with usual care.

Methods

We conducted a phase 3, two-arm, multicentre, parallel-arm, superiority randomised controlled trial with masked outcome assessment, recruiting dyads of people with dementia and sleep disturbance and family carers from community settings. Randomisation to the DREAMS START intervention (plus usual treatment) or usual treatment was conducted at dyadic level, blocked, and stratified by site, with a web-based system assigning allocation. DREAMS START is a six-session, manualised intervention delivered face to face or remotely by non-clinically trained graduates over an approximately 3-month period. The primary outcome was sleep disturbance measured by the Sleep Disorders Inventory (SDI) at 8 months. Analyses were on the intention-to-treat population. This trial is registered with ISRCTN 13072268.

Findings

Between Feb 24, 2021, and March 5, 2023, 377 dyads were randomly assigned (1:1), 189 to usual treatment and 188 to intervention. The mean age of participants with dementia was 79·4 years (SD 9·0), and 206 (55%) were women. The mean SDI score at 8 months was lower in the intervention group compared with the usual treatment group (15·16 [SD 12·77], n=159, vs 20·34 [16·67], n=163]; adjusted difference in means –4·70 [95% CI –7·65 to –1·74], p=0·002). 17 (9%) people with dementia in the intervention group and 17 (9%) in the control group died during the trial; the deaths were unrelated to the intervention.

Interpretation

To our knowledge, DREAMS START is the first multicomponent intervention to improve the sleep of people living at home with dementia more than usual clinical care. It had sustained effectiveness beyond intervention delivery. The intervention’s delivery by non-clinically trained graduates increases the potential for implementation within health services, adding to usual clinical care.

Funding

National Institute for Health and Care Research Health Technology Assessment.
背景:睡眠障碍是痴呆症患者及其家人常见的困扰。非药物干预应作为一线治疗方法,以避免有害的药物副作用,但目前尚无有效的干预方法。我们旨在确定,与常规护理相比,DREAMS START(一种多成分干预措施)是否能减少居家痴呆症患者的睡眠障碍:我们开展了一项第三阶段、双臂、多中心、平行臂、优越性随机对照试验,对结果进行了掩蔽评估,招募了社区中患有痴呆症和睡眠障碍的患者及其家庭照顾者。DREAMS START干预(加常规治疗)或常规治疗的随机分配是在二人一组的基础上进行的,通过网络系统进行分配。DREAMS START 是一项为期六节的人工干预,由未接受过临床培训的毕业生在约三个月的时间内通过面对面或远程的方式进行。主要结果是8个月后通过睡眠障碍量表(SDI)测量的睡眠障碍。分析对象为意向治疗人群。该试验的注册号为 ISRCTN 13072268:2021年2月24日至2023年3月5日期间,377对夫妇被随机分配(1:1),其中189对接受常规治疗,188对接受干预治疗。痴呆症患者的平均年龄为 79-4 岁(SD 9-0),其中 206 人(55%)为女性。与常规治疗组相比,干预组在8个月时的SDI平均得分较低(15-16 [SD 12-77],n=159,vs 20-34 [16-67],n=163];调整后的平均值差异为-4-70 [95% CI -7-65 to -1-74], p=0-002)。干预组中有17名(9%)痴呆症患者在试验期间死亡,对照组中有17名(9%)患者在试验期间死亡,死亡原因与干预无关:据我们所知,"DREAMS START "是第一项多成分干预措施,与常规临床护理相比,它能更有效地改善居家痴呆症患者的睡眠。该干预措施在实施后仍能持续有效。该干预措施由未接受过临床培训的毕业生实施,这增加了在医疗服务中实施的可能性,同时也是对常规临床护理的补充:国家健康与护理研究所健康技术评估。
{"title":"Clinical effectiveness of DREAMS START (Dementia Related Manual for Sleep; Strategies for Relatives) versus usual care for people with dementia and their carers: a single-masked, phase 3, parallel-arm, superiority randomised controlled trial","authors":"Prof Penny Rapaport PhD ,&nbsp;Sarah Amador PhD ,&nbsp;Mariam O Adeleke PhD ,&nbsp;Prof Julie A Barber PhD ,&nbsp;Prof Sube Banerjee MD ,&nbsp;Prof Georgina Charlesworth PhD ,&nbsp;Chris Clarke DClinPsy ,&nbsp;Prof Colin A Espie DSc ,&nbsp;Lina Gonzalez MSc ,&nbsp;Rossana Horsley GradCert ,&nbsp;Prof Rachael Hunter MSc ,&nbsp;Prof Simon D Kyle PhD ,&nbsp;Monica Manela BM ,&nbsp;Malgorzata Raczek PhD ,&nbsp;Prof Zuzana Walker MD ,&nbsp;Lucy Webster PhD ,&nbsp;Hang Yuan PhD ,&nbsp;Prof Gill Livingston MD","doi":"10.1016/j.lanhl.2024.08.004","DOIUrl":"10.1016/j.lanhl.2024.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Sleep disturbances are common and distressing for people with dementia and their families. Non-pharmacological interventions should be first-line management, avoiding harmful pharmacological side-effects, but there is none with known effectiveness. We aimed to establish whether DREAMS START, a multicomponent intervention, reduced sleep disturbance in people with dementia living at home compared with usual care.</div></div><div><h3>Methods</h3><div>We conducted a phase 3, two-arm, multicentre, parallel-arm, superiority randomised controlled trial with masked outcome assessment, recruiting dyads of people with dementia and sleep disturbance and family carers from community settings. Randomisation to the DREAMS START intervention (plus usual treatment) or usual treatment was conducted at dyadic level, blocked, and stratified by site, with a web-based system assigning allocation. DREAMS START is a six-session, manualised intervention delivered face to face or remotely by non-clinically trained graduates over an approximately 3-month period. The primary outcome was sleep disturbance measured by the Sleep Disorders Inventory (SDI) at 8 months. Analyses were on the intention-to-treat population. This trial is registered with ISRCTN 13072268.</div></div><div><h3>Findings</h3><div>Between Feb 24, 2021, and March 5, 2023, 377 dyads were randomly assigned (1:1), 189 to usual treatment and 188 to intervention. The mean age of participants with dementia was 79·4 years (SD 9·0), and 206 (55%) were women. The mean SDI score at 8 months was lower in the intervention group compared with the usual treatment group (15·16 [SD 12·77], n=159, <em>vs</em> 20·34 [16·67], n=163]; adjusted difference in means –4·70 [95% CI –7·65 to –1·74], p=0·002). 17 (9%) people with dementia in the intervention group and 17 (9%) in the control group died during the trial; the deaths were unrelated to the intervention.</div></div><div><h3>Interpretation</h3><div>To our knowledge, DREAMS START is the first multicomponent intervention to improve the sleep of people living at home with dementia more than usual clinical care. It had sustained effectiveness beyond intervention delivery. The intervention’s delivery by non-clinically trained graduates increases the potential for implementation within health services, adding to usual clinical care.</div></div><div><h3>Funding</h3><div>National Institute for Health and Care Research Health Technology Assessment.</div></div>","PeriodicalId":34394,"journal":{"name":"Lancet Healthy Longevity","volume":"5 10","pages":"Article 100635"},"PeriodicalIF":13.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A retinal biomarker of biological age based on composite clinical phenotypic information 基于综合临床表型信息的生物年龄视网膜生物标记。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/S2666-7568(24)00109-0
Ruiyang Li , Haotian Lin
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引用次数: 0
Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease 实际应用阿尔茨海默病血液生物标志物所面临的挑战。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lanhl.2024.07.013
Prof Michael Schöll PhD , Inge M W Verberk PhD , Marta del Campo PhD , Constance Delaby PhD , Joseph Therriault PhD , Joyce R Chong PhD , Sebastian Palmqvist PhD , Daniel Alcolea PhD
Blood biomarkers have emerged as accessible, cost-effective, and highly promising tools for advancing the diagnostics of Alzheimer’s disease. However, transitioning from cerebrospinal fluid biomarkers to blood biomarkers—eg, to verify amyloid β pathology—requires careful consideration. This Series paper highlights the main challenges in the implementation of blood biomarkers for Alzheimer’s disease in different possible contexts of use. Despite the robustness of measuring blood biomarker concentrations, the widespread adoption of blood biomarkers requires rigorous standardisation efforts to address inherent challenges in diverse contexts of use. The challenges include understanding the effect of pre-analytical and analytical conditions, potential confounding factors, and comorbidities that could influence outcomes of blood biomarkers and their use in diverse populations. Additionally, distinct scenarios present their own specific challenges. In memory clinics, the successful integration of blood biomarkers in diagnostic tests will require well-established diagnostic accuracy and comprehensive assessments of the effect of blood biomarkers on the diagnostic confidence and patient management of clinicians. In primary care settings, and even more when implemented in population-based screening programmes for which no experience with any biomarkers for Alzheimer’s disease currently exists, the implementation of blood biomarkers will be challenged by the need for education of primary care clinical staff and clear guidelines. However, despite the challenges, blood biomarkers hold great promise for substantially enhancing the diagnostic accuracy and effectively streamlining referral processes, leading to earlier diagnosis and access to treatments. The ongoing efforts that are shaping the integration of blood biomarkers across diverse clinical settings pave the way towards precision medicine in Alzheimer’s disease.
血液生物标志物已成为可获得的、具有成本效益的、极有希望推动阿尔茨海默病诊断的工具。然而,从脑脊液生物标记物过渡到血液生物标记物--例如,用于验证淀粉样β病理学--需要慎重考虑。这篇系列论文强调了在不同可能的使用环境中实施阿尔茨海默病血液生物标志物所面临的主要挑战。尽管血液生物标记物浓度的测量具有稳健性,但血液生物标记物的广泛采用需要严格的标准化工作,以应对不同使用环境中固有的挑战。这些挑战包括了解分析前和分析条件、潜在混杂因素以及合并症的影响,这些因素可能会影响血液生物标志物的结果及其在不同人群中的使用。此外,不同的情况也会带来各自特定的挑战。在记忆诊所,要成功地将血液生物标记物整合到诊断检测中,就必须确立良好的诊断准确性,并全面评估血液生物标记物对临床医生诊断信心和患者管理的影响。在基层医疗机构,尤其是在目前还没有任何阿尔茨海默病生物标志物经验的人群筛查计划中实施时,血液生物标志物的实施将面临挑战,因为需要对基层医疗机构的临床人员进行教育并制定明确的指导方针。不过,尽管存在这些挑战,血液生物标记物仍有很大的潜力,可大幅提高诊断准确性并有效简化转诊流程,从而更早地做出诊断和获得治疗。血液生物标志物在不同临床环境中的不断应用,为阿尔茨海默病的精准医疗铺平了道路。
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引用次数: 0
Application of a deep-learning marker for morbidity and mortality prediction derived from retinal photographs: a cohort development and validation study 应用深度学习标记对视网膜照片中的发病率和死亡率进行预测:队列开发和验证研究。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/S2666-7568(24)00089-8
Simon Nusinovici PhD , Tyler Hyungtaek Rim MD , Hengtong Li MS , Marco Yu PhD , Mihir Deshmukh MS , Ten Cheer Quek BEng , Geunyoung Lee MS , Crystal Chun Yuen Chong MS , Qingsheng Peng MD , Can Can Xue PhD , Zhuoting Zhu MD , Emily Y Chew MD , Charumathi Sabanayagam PhD , Prof Tien-Yin Wong PhD , Yih-Chung Tham PhD , Prof Ching-Yu Cheng MD
<div><h3>Background</h3><div>Biological ageing markers are useful to risk stratify morbidity and mortality more precisely than chronological age. In this study, we aimed to develop a novel deep-learning-based biological ageing marker (referred to as RetiPhenoAge hereafter) using retinal images and PhenoAge, a composite biomarker of phenotypic age.</div></div><div><h3>Methods</h3><div>We used retinal photographs from the UK Biobank dataset to train a deep-learning algorithm to predict the composite score of PhenoAge. We used a deep convolutional neural network architecture with multiple layers to develop our deep-learning-based biological ageing marker, as RetiPhenoAge, with the aim of identifying patterns and features in the retina associated with variations of blood biomarkers related to renal, immune, liver functions, inflammation, and energy metabolism, and chronological age. We determined the performance of this biological ageing marker for the prediction of morbidity (cardiovascular disease and cancer events) and mortality (all-cause, cardiovascular disease, and cancer) in three independent cohorts (UK Biobank, the Singapore Epidemiology of Eye Diseases [SEED], and the Age-Related Eye Disease Study [AREDS] from the USA). We also compared the performance of RetiPhenoAge with two other known ageing biomarkers (hand grip strength and adjusted leukocyte telomere length) and one lifestyle factor (physical activity) for risk stratification of mortality and morbidity. We explored the underlying biology of RetiPhenoAge by assessing its associations with different systemic characteristics (eg, diabetes or hypertension) and blood metabolite levels. We also did a genome-wide association study to identify genetic variants associated with RetiPhenoAge, followed by expression quantitative trait loci mapping, a gene-based analysis, and a gene-set analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and corresponding 95% CIs for the associations between RetiPhenoAge and the different morbidity and mortality outcomes.</div></div><div><h3>Findings</h3><div>Retinal photographs for 34 061 UK Biobank participants were used to train the model, and data for 9429 participants from the SEED cohort and for 3986 participants from the AREDS cohort were included in the study. RetiPhenoAge was associated with all-cause mortality (HR 1·92 [95% CI 1·42–2·61]), cardiovascular disease mortality (1·97 [1·02–3·82]), cancer mortality (2·07 [1·29–3·33]), and cardiovascular disease events (1·70 [1·17–2·47]), independent of PhenoAge and other possible confounders. Similar findings were found in the two independent cohorts (HR 1·67 [1·21–2·31] for cardiovascular disease mortality in SEED and 2·07 [1·10–3·92] in AREDS). RetiPhenoAge had stronger associations with mortality and morbidity than did hand grip strength, telomere length, and physical activity. We identified two genetic variants that were significantly associated with RetiPhenoAge (single
背景:生物老化标志物比计时年龄更有助于对发病率和死亡率进行风险分层。在本研究中,我们旨在利用视网膜图像和表型年龄的复合生物标志物 PhenoAge,开发一种基于深度学习的新型生物老化标志物(以下简称为 RetiPhenoAge):我们使用英国生物库数据集中的视网膜照片来训练一种深度学习算法,以预测 PhenoAge 的综合得分。我们使用多层深度卷积神经网络架构来开发基于深度学习的生物年龄标记,即 RetiPhenoAge,目的是识别视网膜中与肾脏、免疫、肝功能、炎症和能量代谢相关的血液生物标记物的变化以及实际年龄有关的模式和特征。我们在三个独立的队列(英国生物库、新加坡眼病流行病学研究[SEED]和美国年龄相关眼病研究[AREDS])中确定了这一生物老化标志物在预测发病率(心血管疾病和癌症事件)和死亡率(全因、心血管疾病和癌症)方面的性能。我们还比较了 RetiPhenoAge 与另外两个已知的老化生物标志物(手部握力和调整后的白细胞端粒长度)和一个生活方式因素(体育锻炼)在死亡率和发病率风险分层方面的表现。我们通过评估 RetiPhenoAge 与不同系统特征(如糖尿病或高血压)和血液代谢物水平的关联,探索了 RetiPhenoAge 的潜在生物学特性。我们还进行了一项全基因组关联研究,以确定与 RetiPhenoAge 相关的遗传变异,随后进行了表达量性状位点图绘制、基于基因的分析和基因组分析。研究采用 Cox 比例危险模型来估算 RetiPhenoAge 与不同发病率和死亡率之间关系的危险比(HRs)和相应的 95% CI:34 061 名英国生物库参与者的视网膜照片被用于训练模型,SEED 队列中 9429 名参与者和 AREDS 队列中 3986 名参与者的数据被纳入研究。RetiPhenoAge与全因死亡率(HR 1-92 [95% CI 1-42-2-61])、心血管疾病死亡率(1-97 [1-02-3-82])、癌症死亡率(2-07 [1-29-3-33])和心血管疾病事件(1-70 [1-17-2-47])相关,与PhenoAge和其他可能的混杂因素无关。在两个独立的队列中也发现了类似的结果(SEED 的心血管疾病死亡率 HR 为 1-67 [1-21-2-31],AREDS 为 2-07 [1-10-3-92])。与手部握力、端粒长度和体力活动相比,RetiPhenoAge 与死亡率和发病率的关系更为密切。我们发现了两个与 RetiPhenoAge 显著相关的基因变异(单核苷酸多态性 rs3791224 和 rs8001273),它们与心脏、肾脏和大脑等不同组织的表达量性状位点相关:我们新的深度学习衍生生物老化标记是预测死亡率和发病率结果的可靠指标,可用作测量老化的新型无创方法:新加坡国家医学研究理事会和新加坡科技研究局。
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引用次数: 0
Long-term air pollution exposure and incident physical disability in older US adults: a cohort study 美国老年人长期暴露于空气污染与身体残疾事件:一项队列研究。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.lanhl.2024.07.012
Jiaqi Gao PhD , Carlos F Mendes de Leon PhD , Boya Zhang PhD , Jennifer Weuve ScD , Kenneth M Langa PhD , Jennifer D'Souza PhD , Adam Szpiro PhD , Jessica Faul PhD , Joel D Kaufman MD , Richard Hirth PhD , Sara D Adar ScD

Background

Disability is a key marker of overall physical health in older adults and is often preceded by chronic disease. Although air pollution is a well recognised risk factor for multiple chronic diseases, its association with physical disability has not been well characterised. We investigated the associations of air pollutants with physical disability in a large cohort representative of older adults in the USA.

Methods

We used biennial data on incident activities of daily living (ADL) disability collected from respondents of the Health and Retirement Survey between 2000 and 2016. As part of the Environmental Predictors of Cognitive Health and Aging study, we estimated 10-year average PM2·5, PM102·5, nitrogen dioxide (NO2), and ozone (O3) concentrations at participant residences before each survey using spatiotemporal prediction models. We used a time-varying, weighted Cox model to estimate hazard ratios (HRs) for incident physical disability per interquartile increase of air pollution with detailed adjustments for confounders.

Findings

Among 15 411 respondents aged 65 years and older (mean age 70·2 [SD 6·5] years; 55% female, 45% male), 48% of respondents reported newly having ADL disability during a mean follow-up of 7·9 years (SD 4·7). In fully adjusted models, we found greater risks of ADL disability associated with higher concentrations of PM2·5 (HR 1·03 per 3·7 μg/m³ [95% CI 0·99–1·08], p=0·16), PM102·5 (1·05 per 4·9 μg/m³ [1·00–1·11], p=0·022), and NO2 (1·03 per 7·5 ppb [0·99–1·08]. p=0·064), although not all these associations were statistically significant. In contrast, O3 was associated with a lower risk of ADL disability (0·95 per 3·7 ppb [0·91–1·00], p=0·030). In a multi-pollutant model, associations were similar to the single-pollutant models for PM102·5 (1·05 per 4·9 μg/m³ [1·00–1·11], p=0·041) and O3 (0·94 per 3·7 ppb [0·88–1·01], p=0·083).

Interpretation

Our findings suggest that air pollution might be an underappreciated risk factor for physical disability in later life, although additional research is needed.

Funding

National Institutes of Environmental Health Sciences and National Institute on Aging.
背景:残疾是老年人整体身体健康的一个重要标志,而且往往先于慢性疾病。虽然空气污染是公认的多种慢性疾病的风险因素,但它与身体残疾的关系还没有得到很好的描述。我们在美国一个具有代表性的老年人大型队列中调查了空气污染物与身体残疾的关系:我们使用了 2000 年至 2016 年期间从健康与退休调查(Health and Retirement Survey)受访者处收集的两年一次的日常生活活动(ADL)残疾事件数据。作为认知健康和老龄化环境预测研究的一部分,我们使用时空预测模型估算了每次调查前受访者住所的 PM2-5、PM10-2-5、二氧化氮(NO2)和臭氧(O3)的 10 年平均浓度。我们使用时变加权 Cox 模型估算了空气污染每增加四分位数所导致的身体残疾的危险比(HRs),并对混杂因素进行了详细调整:在 15 411 名 65 岁及以上的受访者中(平均年龄 70-2 [SD 6-5] 岁;55% 为女性,45% 为男性),48% 的受访者表示在平均 7-9 年(SD 4-7 年)的随访期间新近出现了 ADL 残疾。在完全调整模型中,我们发现,PM2-5(HR 1-03 per 3-7 μg/m³ [95% CI 0-99-1-08],p=0-16)、PM10-2-5(1-05 per 4-9 μg/m³ [1-00-1-11],p=0-022)和 NO2(1-03 per 7-5 ppb [0-99-1-08],p=0-064)浓度越高,ADL 残疾的风险越大,但并非所有这些关联都具有统计学意义。相比之下,O3 与较低的 ADL 残疾风险相关(每 3-7 ppb 0-95 [0-91-1-00],p=0-030)。在多污染物模型中,PM10-2-5(1-05 per 4-9 μg/m³ [1-00-1-11],p=0-041)和臭氧(0-94 per 3-7 ppb [0-88-1-01],p=0-083)的相关性与单污染物模型相似:我们的研究结果表明,空气污染可能是导致晚年身体残疾的一个未被充分重视的风险因素,尽管还需要更多的研究:国家环境健康科学研究所和国家老龄化研究所。
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引用次数: 0
Biomarkers of neurodegeneration across the Global South 全球南部神经变性的生物标志物。
IF 13.4 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-10-01 DOI: 10.1016/S2666-7568(24)00132-6
Eimear McGlinchey PhD , Claudia Duran-Aniotz PhD , Prof Rufus Akinyemi MD , Faheem Arshad MD , Eduardo R Zimmer PhD , Hanna Cho MD , Boluwatife Adeleye Adewale MD , Agustin Ibanez PhD
Research on neurodegenerative diseases has predominantly focused on high-income countries in the Global North. This Series paper describes the state of biomarker evidence for neurodegeneration in the Global South, including Latin America, Africa, and countries in south, east, and southeast Asia. Latin America shows growth in fluid biomarker and neuroimaging research, with notable advancements in genetics. Research in Africa focuses on genetics and cognition but there is a paucity of data on fluid and neuroimaging biomarkers. South and east Asia, particularly India and China, has achieved substantial progress in plasma, neuroimaging, and genetic studies. However, all three regions face several challenges in the form of a lack of harmonisation, insufficient funding, and few comparative studies both within the Global South, and between the Global North and Global South. Other barriers include scarce infrastructure, lack of knowledge centralisation, genetic and cultural diversity, sociocultural stigmas, and restricted access to tools such as PET scans. However, the diverse ethnic, genetic, economic, and cultural backgrounds in the Global South present unique opportunities for bidirectional learning, underscoring the need for global collaboration to enhance the understanding of dementia and brain health.
有关神经退行性疾病的研究主要集中在全球北方的高收入国家。本系列论文介绍了全球南部(包括拉丁美洲、非洲以及南亚、东亚和东南亚国家)神经变性生物标志物证据的现状。拉丁美洲在流体生物标志物和神经影像学研究方面取得了增长,在遗传学方面也取得了显著进展。非洲的研究重点是遗传学和认知,但有关体液和神经影像生物标志物的数据很少。南亚和东亚,尤其是印度和中国,在血浆、神经影像学和遗传学研究方面取得了重大进展。然而,这三个地区都面临着一些挑战,如缺乏统一性、资金不足、全球南部内部以及全球北部和全球南部之间的比较研究很少。其他障碍包括基础设施匮乏、知识缺乏集中性、遗传和文化多样性、社会文化污名以及 PET 扫描等工具的使用受到限制。然而,全球南方国家不同的种族、遗传、经济和文化背景为双向学习提供了独特的机会,突出了全球合作的必要性,以增进对痴呆症和大脑健康的了解。
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引用次数: 0
期刊
Lancet Healthy Longevity
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