Pub Date : 2025-11-19DOI: 10.1016/j.arr.2025.102952
Haolin Yin , Zihao Lu , Yuepeng Deng , Xiaohe Tian , Qiyong Gong
Alzheimer's disease (AD), a leading neurodegenerative disorder, involves blood-brain barrier (BBB) dysfunction as a critical contributor to its pathogenesis. This review synthesizes current advancements in in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques for imaging BBB breakdown in AD. The BBB, a dynamic neurovascular interface, regulates amyloid-beta (Aβ) and tau clearance through specialized transporters and cellular interactions. BBB dysfunction, driven by tight junction disruption, transporter deficits, and pericyte degeneration, exacerbates Aβaccumulation and neuroinflammation. Dynamic contrast-enhanced MRI quantifies subtle leakage via gadolinium kinetics, while water-exchange MRI probes trans-BBB water dynamics without contrast agents. Dynamic glucose-enhanced MRI maps glucose transport anomalies linked to glucose transporter- 1 dysfunction. PET imaging with tracers like [18F]-fluorodeoxyglucose and [11C]-verapamil evaluates glucose metabolism and efflux transporter activity, revealing early metabolic deficits and impaired Aβ clearance. Challenges include low sensitivity for subtle leakage, model-dependent quantification, and spatial-temporal resolution trade-offs. Emerging strategies emphasize multimodal integration, ultrahigh-field systems, and artificial intelligence-driven analytics to decode region-specific BBB pathology. Longitudinal studies correlating imaging biomarkers with clinical progression and novel PET tracer development are pivotal for early diagnosis and personalized therapies. These innovations promise to elucidate BBB’s role and promote a paradigm shift in diagnostic and therapeutic strategies from solely targeting amyloid proteins to multi-target interventions in AD.
阿尔茨海默病（AD）是一种主要的神经退行性疾病，血脑屏障（BBB）功能障碍是其发病机制的关键因素。本文综述了体内磁共振成像（MRI）和正电子发射断层扫描（PET）技术在AD患者血脑屏障破裂成像方面的最新进展。血脑屏障是一个动态的神经血管界面，通过专门的转运蛋白和细胞相互作用调节淀粉样蛋白- β (a β)和tau蛋白的清除。血脑屏障功能障碍，由紧密连接破坏，转运蛋白缺陷和周细胞变性驱动，加剧了a β积累和神经炎症。动态对比增强MRI通过钆动力学量化细微泄漏，而水交换MRI在没有对比剂的情况下探测跨血脑屏障水动力学。动态葡萄糖增强MRI绘制与葡萄糖转运蛋白- 1功能障碍相关的葡萄糖转运异常。用[18F]-氟脱氧葡萄糖和[11C]-维拉帕米等示踪剂进行PET成像可评估葡萄糖代谢和外排转运蛋白活性，揭示早期代谢缺陷和Aβ清除受损。挑战包括对细微泄漏的低灵敏度、依赖模型的量化和时空分辨率的权衡。新兴的策略强调多模式集成、超高场系统和人工智能驱动的分析，以解码特定区域的血脑屏障病理。将成像生物标志物与临床进展和新型PET示踪剂开发相关的纵向研究对于早期诊断和个性化治疗至关重要。这些创新有望阐明血脑屏障的作用，并促进AD诊断和治疗策略的范式转变，从单纯靶向淀粉样蛋白到多靶点干预。
{"title":"Decoding blood-brain barrier dysfunction in Alzheimer's Disease: Innovations and challenges in multimodal MRI and PET imaging biomarkers","authors":"Haolin Yin , Zihao Lu , Yuepeng Deng , Xiaohe Tian , Qiyong Gong","doi":"10.1016/j.arr.2025.102952","DOIUrl":"10.1016/j.arr.2025.102952","url":null,"abstract":"<div><div>Alzheimer's disease (AD), a leading neurodegenerative disorder, involves blood-brain barrier (BBB) dysfunction as a critical contributor to its pathogenesis. This review synthesizes current advancements in in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques for imaging BBB breakdown in AD. The BBB, a dynamic neurovascular interface, regulates amyloid-beta (Aβ) and tau clearance through specialized transporters and cellular interactions. BBB dysfunction, driven by tight junction disruption, transporter deficits, and pericyte degeneration, exacerbates Aβaccumulation and neuroinflammation. Dynamic contrast-enhanced MRI quantifies subtle leakage via gadolinium kinetics, while water-exchange MRI probes trans-BBB water dynamics without contrast agents. Dynamic glucose-enhanced MRI maps glucose transport anomalies linked to glucose transporter- 1 dysfunction. PET imaging with tracers like [<sup>18</sup>F]-fluorodeoxyglucose and [<sup>11</sup>C]-verapamil evaluates glucose metabolism and efflux transporter activity, revealing early metabolic deficits and impaired Aβ clearance. Challenges include low sensitivity for subtle leakage, model-dependent quantification, and spatial-temporal resolution trade-offs. Emerging strategies emphasize multimodal integration, ultrahigh-field systems, and artificial intelligence-driven analytics to decode region-specific BBB pathology. Longitudinal studies correlating imaging biomarkers with clinical progression and novel PET tracer development are pivotal for early diagnosis and personalized therapies. These innovations promise to elucidate BBB’s role and promote a paradigm shift in diagnostic and therapeutic strategies from solely targeting amyloid proteins to multi-target interventions in AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"114 ","pages":"Article 102952"},"PeriodicalIF":12.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fall detection systems are crucial for ensuring the safety of older adults, given the potential for severe injuries resulting from falls. However, developing accurate and reliable detection methods faces challenges due to the rarity of fall events and limited training data. This review provides an in-depth examination of recent progress in fall detection technologies for older adults, with particular attention to addressing the scarcity of data. This review is novel in that it integrates regulatory frameworks for AI-driven systems; spans diverse fields, including engineering, computer science, and gerontology; and establishes clear connections between fall detection and conditions such as osteoporosis and neurological disorders. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to select articles on sensor- and vision-based methodologies and machine learning (ML) algorithms for fall detection. Research findings indicate several strengths, weaknesses, and areas where accuracy can be improved, specifically for older adults. This study introduces a taxonomy that categorizes fall detection methods according to the availability of data during classifier training, thereby providing a clearer understanding of the specific challenges these methods address. Some major findings include the effectiveness achieved through sensor fusion and machine learning, aimed at improving accuracy in detecting falls, especially when sparse data are available. Future research should explore novel sensor modalities, wearable integration, and real-time enhancements to machine learning models. Moreover, this review advances the development of robust AI-based fall detection systems for older adults by addressing key technical challenges and outlining pathways toward clinical translation and regulatory approval to enhance safety and quality of life in an aging society.
{"title":"Artificial intelligence for fall detection in older adults: A comprehensive survey of machine learning, deep learning approaches, and future directions","authors":"Akshat Gattani, Shriniket Dixit, Mrudul Patil, Mehul Gupta, Atharva Navghane, Onkar Hule, Kathiravan Srinivasan","doi":"10.1016/j.arr.2025.102948","DOIUrl":"10.1016/j.arr.2025.102948","url":null,"abstract":"<div><div>Fall detection systems are crucial for ensuring the safety of older adults, given the potential for severe injuries resulting from falls. However, developing accurate and reliable detection methods faces challenges due to the rarity of fall events and limited training data. This review provides an in-depth examination of recent progress in fall detection technologies for older adults, with particular attention to addressing the scarcity of data. This review is novel in that it integrates regulatory frameworks for AI-driven systems; spans diverse fields, including engineering, computer science, and gerontology; and establishes clear connections between fall detection and conditions such as osteoporosis and neurological disorders. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to select articles on sensor- and vision-based methodologies and machine learning (ML) algorithms for fall detection. Research findings indicate several strengths, weaknesses, and areas where accuracy can be improved, specifically for older adults. This study introduces a taxonomy that categorizes fall detection methods according to the availability of data during classifier training, thereby providing a clearer understanding of the specific challenges these methods address. Some major findings include the effectiveness achieved through sensor fusion and machine learning, aimed at improving accuracy in detecting falls, especially when sparse data are available. Future research should explore novel sensor modalities, wearable integration, and real-time enhancements to machine learning models. Moreover, this review advances the development of robust AI-based fall detection systems for older adults by addressing key technical challenges and outlining pathways toward clinical translation and regulatory approval to enhance safety and quality of life in an aging society.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102948"},"PeriodicalIF":12.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1016/j.arr.2025.102946
Matthew J. Johnston , Holly M. Brown-Borg
The gap between lifespan and healthspan is increasing globally, resulting in millions of individuals spending additional years burdened by frailty or disease. This disparity, paired with the increasingly aged populations of Western nations, poses a palpable predicament to public health and the economy. Deterioration of the skeletal muscle system is a key contributor to illness, loss of independence, and diminishing healthspan. Muscle quality correlates to longevity due to its significant role in metabolic homeostasis and autonomous mobility, reducing instances of adverse events such as falls and fractures. The age-related loss of muscle mass and function is termed sarcopenia, affecting older adults ubiquitously without intervention through regular resistance training. Although clinical manifestations of sarcopenia are well characterized, the molecular mechanisms underlying its pathogenesis remain incompletely understood, limiting the development of targeted, mechanism-based interventions. To identify interventions beyond exercise that delay sarcopenia, it is necessary to identify early onset physiological alterations defining this process. Genetically modified mouse models of accelerated or delayed aging offer valuable insight into the cellular mechanisms that drive or mitigate sarcopenia. The latter is often achieved by disrupting the somatotropic axis, as multiple models exist that either lack growth hormone (GH) production or a functional GH receptor (GHR) paired with a secondary deficiency in insulin like growth factor-1 (IGF-1), which reliably extends lifespan across various species. This review evaluates GH’s paradoxical role in muscular maintenance and contrasts the skeletal muscle health of various murine models of aging in effort to better outline the molecular underpinnings of sarcopenia.
{"title":"Utilizing accelerated and delayed murine models of aging to address the “healthspan issue” – A review of skeletal muscle health","authors":"Matthew J. Johnston , Holly M. Brown-Borg","doi":"10.1016/j.arr.2025.102946","DOIUrl":"10.1016/j.arr.2025.102946","url":null,"abstract":"<div><div>The gap between lifespan and healthspan is increasing globally, resulting in millions of individuals spending additional years burdened by frailty or disease. This disparity, paired with the increasingly aged populations of Western nations, poses a palpable predicament to public health and the economy. Deterioration of the skeletal muscle system is a key contributor to illness, loss of independence, and diminishing healthspan. Muscle quality correlates to longevity due to its significant role in metabolic homeostasis and autonomous mobility, reducing instances of adverse events such as falls and fractures. The age-related loss of muscle mass and function is termed sarcopenia, affecting older adults ubiquitously without intervention through regular resistance training. Although clinical manifestations of sarcopenia are well characterized, the molecular mechanisms underlying its pathogenesis remain incompletely understood, limiting the development of targeted, mechanism-based interventions. To identify interventions beyond exercise that delay sarcopenia, it is necessary to identify early onset physiological alterations defining this process. Genetically modified mouse models of accelerated or delayed aging offer valuable insight into the cellular mechanisms that drive or mitigate sarcopenia. The latter is often achieved by disrupting the somatotropic axis, as multiple models exist that either lack growth hormone (GH) production or a functional GH receptor (GHR) paired with a secondary deficiency in insulin like growth factor-1 (IGF-1), which reliably extends lifespan across various species. This review evaluates GH’s paradoxical role in muscular maintenance and contrasts the skeletal muscle health of various murine models of aging in effort to better outline the molecular underpinnings of sarcopenia.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102946"},"PeriodicalIF":12.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.arr.2025.102945
Francesco Sciancalepore , Simone Salemme , Martina Valletta , Marco Toccaceli Blasi , Giulia Remoli , Giovanna Zamboni , Nicola Vanacore , Marco Canevelli
Frailty influences the risk, phenotypic expression, and course of highly prevalent neurological conditions. However, the structural, functional, and pathological changes in the brain associated with frailty remain insufficiently explored. This narrative review examines existing evidence on the functional and pathological brain correlates of frailty in both healthy adults and patients with neurological conditions, encompassing findings from neuropathology, fluid biomarkers, neuroimaging, and neurophysiology. Autopsy studies suggest that individuals experiencing frailty may exhibit decreased resistance and resilience to neuropathological changes, along with heightened cognitive vulnerability, even in the presence of low levels of pathology. The accumulation of brain pathology may, in turn, play a role in accelerating frailty progression. Numerous MRI-based studies have shown that frailty is associated with vascular brain damage, mostly consisting of increased white matter hyperintensity volumes, and with reduced gray matter volumes. Additionally, variations in cerebrospinal fluid and plasma biomarkers of Alzheimer’s disease pathology have been documented. Furthermore, frailty-related changes in EEG/MEG signals and brain plasticity suggest potential widespread neural dysfunction. Future research is needed to elucidate the pathophysiological mechanisms underlying the neurological correlates of frailty. This exploration should encompass key aspects of aging, such as inflammation, mitochondrial dysfunction, and impaired proteostasis. Gaining a deeper understanding of the relationship between frailty and brain function and pathology could pave the way for discovering novel biomarkers and intervention targets, ultimately impacting the prevention and management of age-related neurological conditions.
{"title":"Frailty and the brain: A narrative review of functional and pathological correlates","authors":"Francesco Sciancalepore , Simone Salemme , Martina Valletta , Marco Toccaceli Blasi , Giulia Remoli , Giovanna Zamboni , Nicola Vanacore , Marco Canevelli","doi":"10.1016/j.arr.2025.102945","DOIUrl":"10.1016/j.arr.2025.102945","url":null,"abstract":"<div><div>Frailty influences the risk, phenotypic expression, and course of highly prevalent neurological conditions. However, the structural, functional, and pathological changes in the brain associated with frailty remain insufficiently explored. This narrative review examines existing evidence on the functional and pathological brain correlates of frailty in both healthy adults and patients with neurological conditions, encompassing findings from neuropathology, fluid biomarkers, neuroimaging, and neurophysiology. Autopsy studies suggest that individuals experiencing frailty may exhibit decreased resistance and resilience to neuropathological changes, along with heightened cognitive vulnerability, even in the presence of low levels of pathology. The accumulation of brain pathology may, in turn, play a role in accelerating frailty progression. Numerous MRI-based studies have shown that frailty is associated with vascular brain damage, mostly consisting of increased white matter hyperintensity volumes, and with reduced gray matter volumes. Additionally, variations in cerebrospinal fluid and plasma biomarkers of Alzheimer’s disease pathology have been documented. Furthermore, frailty-related changes in EEG/MEG signals and brain plasticity suggest potential widespread neural dysfunction. Future research is needed to elucidate the pathophysiological mechanisms underlying the neurological correlates of frailty. This exploration should encompass key aspects of aging, such as inflammation, mitochondrial dysfunction, and impaired proteostasis. Gaining a deeper understanding of the relationship between frailty and brain function and pathology could pave the way for discovering novel biomarkers and intervention targets, ultimately impacting the prevention and management of age-related neurological conditions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102945"},"PeriodicalIF":12.4,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.arr.2025.102944
Lin Chen , Kai Zhang , Xiaoli Liu , Yushi Fan , Xinyun Zhang , Sheng Zhang , Xuehuan Wen , Songjie Bai , Qing Wang , Wei Cui , Zhongheng Zhang , Minfeng Tong , Gensheng Zhang
Background
Infectious diseases caused by bacterial and viral pathogens remain major contributors to global mortality and disease burden, especially for older adults. Despite progress in disease control, the pathogen-specific burden across multiple disease categories, especially among the elderly population, has not been comprehensively quantified. This study estimates the global and regional burden of 34 key pathogens in 2021, with a specific focus on mortality and disability-adjusted life years (DALYs) in older adults.
Method
This study utilized data from the Global Burden of Disease (GBD) 2021 study to estimate mortality and DALYs attributable to 34 key bacterial and viral pathogens across 204 countries and territories. Pathogen-specific contributions were determined using the GBD comparative risk assessment framework and cause-of-death ensemble modeling. Age-standardized death and DALYs rate were calculated, and variations were examined across Socio-demographic Index (SDI) categories and geographic regions. Uncertainty intervals (UIs) were generated through Monte Carlo simulations.
Findings
In 2021, Staphylococcus aureus was the leading pathogen, responsible for 325,165 deaths (95 % UI: 281,827–356,269) and 4766,188 DALYs (95 % UI 4218,780–5202,881), with age-standardized rate of 32.40 death (95 % UI 27.94–35.53) and 459.37 DALYs (95 % UI 404.90–501.85) per 100,000 population. Pathogens such as Respiratory syncytial virus, Enteropathogenic E. coli, and Aeromonas caused the least global burden. Regionally, Staphylococcus aureus was the primary cause of mortality and DALYs in 15 of 21 GBD regions, with the highest mortality in Eastern Sub-Saharan Africa and the highest DALYs rate in Southern Sub-Saharan Africa. Streptococcus pneumoniae and Staphylococcus aureus were the leading contributors to infectious disease burden in elder populations, with their impact increasing with age. A strong inverse correlation was observed between SDI and age-standardized rate of death and DALYs, with lower SDI regions, such as Sub-Saharan Africa, bearing the highest burden.
Interpretation
This study highlights the disproportionate impact of infectious pathogens on older adults, particularly in low-SDI regions, and underscores the need for targeted interventions, resource allocation, and healthcare improvements to address this growing public health challenge. These findings provide critical insights to inform global strategies for reducing pathogen-related mortality and disability among the elderly population.
{"title":"Global and regional burden of 34 key pathogens in the elderly population in 2021: A systematic analysis of the global burden of disease study 2021","authors":"Lin Chen , Kai Zhang , Xiaoli Liu , Yushi Fan , Xinyun Zhang , Sheng Zhang , Xuehuan Wen , Songjie Bai , Qing Wang , Wei Cui , Zhongheng Zhang , Minfeng Tong , Gensheng Zhang","doi":"10.1016/j.arr.2025.102944","DOIUrl":"10.1016/j.arr.2025.102944","url":null,"abstract":"<div><h3>Background</h3><div>Infectious diseases caused by bacterial and viral pathogens remain major contributors to global mortality and disease burden, especially for older adults. Despite progress in disease control, the pathogen-specific burden across multiple disease categories, especially among the elderly population, has not been comprehensively quantified. This study estimates the global and regional burden of 34 key pathogens in 2021, with a specific focus on mortality and disability-adjusted life years (DALYs) in older adults.</div></div><div><h3>Method</h3><div>This study utilized data from the Global Burden of Disease (GBD) 2021 study to estimate mortality and DALYs attributable to 34 key bacterial and viral pathogens across 204 countries and territories. Pathogen-specific contributions were determined using the GBD comparative risk assessment framework and cause-of-death ensemble modeling. Age-standardized death and DALYs rate were calculated, and variations were examined across Socio-demographic Index (SDI) categories and geographic regions. Uncertainty intervals (UIs) were generated through Monte Carlo simulations.</div></div><div><h3>Findings</h3><div>In 2021, <em>Staphylococcus aureus</em> was the leading pathogen, responsible for 325,165 deaths (95 % UI: 281,827–356,269) and 4766,188 DALYs (95 % UI 4218,780–5202,881), with age-standardized rate of 32.40 death (95 % UI 27.94–35.53) and 459.37 DALYs (95 % UI 404.90–501.85) per 100,000 population. Pathogens such as <em>Respiratory syncytial virus</em>, <em>Enteropathogenic E. coli</em>, and <em>Aeromonas</em> caused the least global burden. Regionally, <em>Staphylococcus aureus</em> was the primary cause of mortality and DALYs in 15 of 21 GBD regions, with the highest mortality in Eastern Sub-Saharan Africa and the highest DALYs rate in Southern Sub-Saharan Africa. <em>Streptococcus pneumoniae</em> and <em>Staphylococcus aureus</em> were the leading contributors to infectious disease burden in elder populations, with their impact increasing with age. A strong inverse correlation was observed between SDI and age-standardized rate of death and DALYs, with lower SDI regions, such as Sub-Saharan Africa, bearing the highest burden.</div></div><div><h3>Interpretation</h3><div>This study highlights the disproportionate impact of infectious pathogens on older adults, particularly in low-SDI regions, and underscores the need for targeted interventions, resource allocation, and healthcare improvements to address this growing public health challenge. These findings provide critical insights to inform global strategies for reducing pathogen-related mortality and disability among the elderly population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102944"},"PeriodicalIF":12.4,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.arr.2025.102941
Upasana Mukherjee , Malcolm Brownell , P. Hemachandra Reddy
Dementia is an escalating global public health challenge, with India poised to experience one of the largest absolute increases in cases due to rapid demographic aging, lifestyle transitions, and health system constraints. This review critically examines the epidemiology, barriers to diagnosis and care, economic and social impacts, and proposes an integrated dementia care framework for India. While dementia has traditionally been viewed through a social and clinical lens, emerging evidence highlights the biological complexity underlying its onset and progression. The interplay of hallmark mechanisms of aging—including amyloid-β and tau pathology, mitochondrial dysfunction, neuroinflammation, and loss of proteostasis—forms the foundation of dementia pathogenesis. Additionally, systemic factors such as metabolic dysregulation, gut–brain axis disruption, and chronic inflammation further amplify neurodegeneration. Sleep deprivation, a modifiable risk factor, accelerates amyloid deposition, brain atrophy, and cognitive decline, while comorbid conditions like diabetes, cardiovascular disease, and depression compound vulnerability. Lifestyle interventions, including physical activity, healthy diet and sleep optimization, alongside novel therapeutic avenues such as psychedelic-assisted interventions, offer promising strategies for prevention and care. Drawing insights from global models, we propose a tiered network of dementia centers in India, integrating mechanistic knowledge with community-based care, early detection, caregiver support, and culturally tailored interventions. Further, it is an opportunity for private Indian Hospitals such as Apollo Research Academy and others to develop Dementia Centers in India. These approaches emphasize the prevention across the life course, equity in access, and sustainability in implementation. A dementia-inclusive strategy for India must align biological insights with policy innovation to mitigate the impending burden and safeguard cognitive health in an aging population.
痴呆症是一项不断升级的全球公共卫生挑战，由于人口快速老龄化、生活方式转变和卫生系统限制，印度有望成为病例绝对增幅最大的国家之一。本综述严格审查了流行病学、诊断和护理障碍、经济和社会影响，并为印度提出了一个综合痴呆症护理框架。虽然痴呆症传统上是通过社会和临床角度来看待的，但新出现的证据强调了其发病和进展背后的生物学复杂性。衰老的标志机制（包括淀粉样蛋白-β和tau病理学、线粒体功能障碍、神经炎症和蛋白酶丧失）的相互作用构成了痴呆发病的基础。此外，代谢失调、肠-脑轴断裂和慢性炎症等全身性因素进一步放大了神经变性。睡眠不足是一个可改变的风险因素，它会加速淀粉样蛋白沉积、脑萎缩和认知能力下降，而糖尿病、心血管疾病和抑郁症等共病会加剧脆弱性。生活方式干预，包括身体活动、健康饮食和睡眠优化，以及新的治疗途径，如迷幻剂辅助干预，为预防和护理提供了有希望的策略。借鉴全球模式的见解，我们提出了印度痴呆中心的分层网络，将机械知识与社区护理、早期检测、护理人员支持和文化定制干预相结合。此外，这也是Apollo Research Academy等印度私立医院在印度发展痴呆症中心的一个机会。这些方法强调整个生命周期的预防、获得的公平性和实施的可持续性。印度的痴呆症包容性战略必须将生物学见解与政策创新结合起来，以减轻即将到来的负担，并保障老龄化人口的认知健康。
{"title":"Aging, dementia, and care models: Global perspectives with insights from India","authors":"Upasana Mukherjee , Malcolm Brownell , P. Hemachandra Reddy","doi":"10.1016/j.arr.2025.102941","DOIUrl":"10.1016/j.arr.2025.102941","url":null,"abstract":"<div><div>Dementia is an escalating global public health challenge, with India poised to experience one of the largest absolute increases in cases due to rapid demographic aging, lifestyle transitions, and health system constraints. This review critically examines the epidemiology, barriers to diagnosis and care, economic and social impacts, and proposes an integrated dementia care framework for India. While dementia has traditionally been viewed through a social and clinical lens, emerging evidence highlights the biological complexity underlying its onset and progression. The interplay of hallmark mechanisms of aging—including amyloid-β and tau pathology, mitochondrial dysfunction, neuroinflammation, and loss of proteostasis—forms the foundation of dementia pathogenesis. Additionally, systemic factors such as metabolic dysregulation, gut–brain axis disruption, and chronic inflammation further amplify neurodegeneration. Sleep deprivation, a modifiable risk factor, accelerates amyloid deposition, brain atrophy, and cognitive decline, while comorbid conditions like diabetes, cardiovascular disease, and depression compound vulnerability. Lifestyle interventions, including physical activity, healthy diet and sleep optimization, alongside novel therapeutic avenues such as psychedelic-assisted interventions, offer promising strategies for prevention and care. Drawing insights from global models, we propose a tiered network of dementia centers in India, integrating mechanistic knowledge with community-based care, early detection, caregiver support, and culturally tailored interventions. Further, it is an opportunity for private Indian Hospitals such as Apollo Research Academy and others to develop Dementia Centers in India. These approaches emphasize the prevention across the life course, equity in access, and sustainability in implementation. A dementia-inclusive strategy for India must align biological insights with policy innovation to mitigate the impending burden and safeguard cognitive health in an aging population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102941"},"PeriodicalIF":12.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.arr.2025.102940
Massimiliano Fedecostante , Paolo Balietti , Alessia Beccacece , Barbara Carrieri , Massimiliano Orso , Alessandra Coin , Chiara Ceolin , Giuseppe Sergi , Francesca Cecchi , Marco Baccini , Diego Longo , Licia Iacoviello , Rosa Liperoti , Fabrizia Lattanzio , Antonio Cherubini
Background
Older adults with multimorbidity are often excluded from clinical trials. Traditional disease-centered endpoints may be inadequate for this population, presenting unique challenges related to frailty, functional decline and disability.
Objectives
To systematically review the literature on outcomes considered relevant in interventions targeting older adults with multimorbidity, based on both patient and healthcare professionals’ perspectives.
Methods
This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42023478249). We searched five electronic databases for primary quantitative and qualitative studies including patients aged ≥ 60 years with ≥ 2 chronic conditions. Outcomes were categorized into six domains: 1) Physical conditions/outcomes; 2) Mental conditions/outcomes; 3) Psychosocial outcomes/general health; 4) Healthcare utilization and costs; 5) Patients’ behaviors; 6) Care process outcomes. We conducted a narrative synthesis and compared outcomes across qualitative and quantitative studies.
Results
Seventy-one studies were included (53 quantitative, 16 qualitative, 2 mixed-methods). The most frequently reported outcomes fell under Psychosocial outcomes / General health (69.0 %), followed by Care process outcomes (52.1 %) and Healthcare utilization and costs (49.3 %). Qualitative studies more often addressed Mental health outcomes (43.8 %). Maintaining independence, physical function, and quality of life emerged as most important outcomes for older adults.
Conclusions
In intervention studies involving older adults with multimorbidity, outcomes should move beyond disease-specific measures to include independence, physical function and quality of life. Outcome selection should account for patient clinical heterogeneity, frailty, and life expectancy to ensure relevance and impact in this complex population.
{"title":"Outcome measures for health interventions targeting multimorbid older adults: A systematic review","authors":"Massimiliano Fedecostante , Paolo Balietti , Alessia Beccacece , Barbara Carrieri , Massimiliano Orso , Alessandra Coin , Chiara Ceolin , Giuseppe Sergi , Francesca Cecchi , Marco Baccini , Diego Longo , Licia Iacoviello , Rosa Liperoti , Fabrizia Lattanzio , Antonio Cherubini","doi":"10.1016/j.arr.2025.102940","DOIUrl":"10.1016/j.arr.2025.102940","url":null,"abstract":"<div><h3>Background</h3><div>Older adults with multimorbidity are often excluded from clinical trials. Traditional disease-centered endpoints may be inadequate for this population, presenting unique challenges related to frailty, functional decline and disability.</div></div><div><h3>Objectives</h3><div>To systematically review the literature on outcomes considered relevant in interventions targeting older adults with multimorbidity, based on both patient and healthcare professionals’ perspectives.</div></div><div><h3>Methods</h3><div>This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42023478249). We searched five electronic databases for primary quantitative and qualitative studies including patients aged ≥ 60 years with ≥ 2 chronic conditions. Outcomes were categorized into six domains: 1) Physical conditions/outcomes; 2) Mental conditions/outcomes; 3) Psychosocial outcomes/general health; 4) Healthcare utilization and costs; 5) Patients’ behaviors; 6) Care process outcomes. We conducted a narrative synthesis and compared outcomes across qualitative and quantitative studies.</div></div><div><h3>Results</h3><div>Seventy-one studies were included (53 quantitative, 16 qualitative, 2 mixed-methods). The most frequently reported outcomes fell under Psychosocial outcomes / General health (69.0 %), followed by Care process outcomes (52.1 %) and Healthcare utilization and costs (49.3 %). Qualitative studies more often addressed Mental health outcomes (43.8 %). Maintaining independence, physical function, and quality of life emerged as most important outcomes for older adults.</div></div><div><h3>Conclusions</h3><div>In intervention studies involving older adults with multimorbidity, outcomes should move beyond disease-specific measures to include independence, physical function and quality of life. Outcome selection should account for patient clinical heterogeneity, frailty, and life expectancy to ensure relevance and impact in this complex population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102940"},"PeriodicalIF":12.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.arr.2025.102942
Zhuoqi Luo, Haiyan Ren, Lukman Ahmed Wali, Shuo Wang, Fang Zhou
Objective
To systematically investigate the relationship between early life circumstances and multi-system biological aging and to synthesize evidence on mediating and moderating factors.
Methods
Studies from PubMed, EMBASE, Web of Science, Scopus, PsycInfo, CNKI, and SinoMed were searched from inception to February 2025. We included observational studies examining the relationship between early life circumstances (including adverse childhood experiences, childhood socio-economic status, perinatal factors, and childhood personal traits) and multi-system biological aging (composite algorithms based on multi-system clinical biomarkers, such as phenotypic age, Klemera-Doubal method biological age, homeostatic dysregulation, and Pace of Aging). A multi-level random-effects meta-analysis was employed for data synthesis. Sensitivity, moderator, and subgroup analyses were conducted to explore sources of heterogeneity and test robustness.
Results
A total of 23 studies containing 344,852 participants were included. 16 of these were included in a meta-analysis, which showed a statistically significant correlation between early life circumstances and multi-system biological aging (Cohen's d = 0.18, 95 %CI: 0.12–0.24, p < 0.0001). Moderator analysis and subgroup analysis indicated that the type, period, and assessment method of early life circumstances, the multi-system biological aging indicators, age, geographic location, study quality, and covariate adjustment significantly influenced the association. The neighbourhood and living environment was a mediator, while age and sex served as moderators. Socioeconomic status, psychosocial factors, and healthy lifestyles exhibited both mediating and moderating effects.
Conclusions
Adverse early life circumstances are associated with accelerated multi-system biological aging. These findings provide a foundation for identifying at-risk populations and formulating targeted interventions to decelerate biological aging.
目的：系统探讨早期生活环境与多系统生物衰老的关系，并综合相关的调节和调节因素。方法检索PubMed、EMBASE、Web of Science、Scopus、PsycInfo、CNKI、SinoMed等网站自建站至2025年2月的研究。我们纳入了观察性研究，研究了早期生活环境（包括不良童年经历、童年社会经济地位、围产期因素和童年个人特征）与多系统生物衰老（基于多系统临床生物标志物的复合算法，如表型年龄、klemera - double方法生物年龄、体内平衡失调和衰老速度）之间的关系。采用多层级随机效应荟萃分析进行数据综合。进行敏感性、调节因子和亚组分析以探索异质性来源和检验稳健性。结果：共纳入23项研究，344,852名受试者。其中16例纳入了荟萃分析，结果显示，早期生活环境与多系统生物衰老之间存在统计学上显著的相关性(Cohen’s d=0.18, 95%CI: 0.12-0.24, p
{"title":"The association between early life circumstances and multi-system biological aging: A systematic review and meta-analysis","authors":"Zhuoqi Luo, Haiyan Ren, Lukman Ahmed Wali, Shuo Wang, Fang Zhou","doi":"10.1016/j.arr.2025.102942","DOIUrl":"10.1016/j.arr.2025.102942","url":null,"abstract":"<div><h3>Objective</h3><div>To systematically investigate the relationship between early life circumstances and multi-system biological aging and to synthesize evidence on mediating and moderating factors.</div></div><div><h3>Methods</h3><div>Studies from PubMed, EMBASE, Web of Science, Scopus, PsycInfo, CNKI, and SinoMed were searched from inception to February 2025. We included observational studies examining the relationship between early life circumstances (including adverse childhood experiences, childhood socio-economic status, perinatal factors, and childhood personal traits) and multi-system biological aging (composite algorithms based on multi-system clinical biomarkers, such as phenotypic age, Klemera-Doubal method biological age, homeostatic dysregulation, and Pace of Aging). A multi-level random-effects meta-analysis was employed for data synthesis. Sensitivity, moderator, and subgroup analyses were conducted to explore sources of heterogeneity and test robustness.</div></div><div><h3>Results</h3><div>A total of 23 studies containing 344,852 participants were included. 16 of these were included in a meta-analysis, which showed a statistically significant correlation between early life circumstances and multi-system biological aging (Cohen's <em>d</em> = 0.18, 95 %CI: 0.12–0.24, <em>p</em> < 0.0001). Moderator analysis and subgroup analysis indicated that the type, period, and assessment method of early life circumstances, the multi-system biological aging indicators, age, geographic location, study quality, and covariate adjustment significantly influenced the association. The neighbourhood and living environment was a mediator, while age and sex served as moderators. Socioeconomic status, psychosocial factors, and healthy lifestyles exhibited both mediating and moderating effects.</div></div><div><h3>Conclusions</h3><div>Adverse early life circumstances are associated with accelerated multi-system biological aging. These findings provide a foundation for identifying at-risk populations and formulating targeted interventions to decelerate biological aging.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102942"},"PeriodicalIF":12.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.arr.2025.102939
Xi Cheng , Qiao-Yu Fu , Yun-Ling Zheng , Gennadiy P. Moiseyev , Fang-Chi Hsu , Jian-Xing Ma , Qing-Feng Li , Anthony Atala , Yuan-Yuan Zhang
Aging is a complex process that leads to various pathologies and poses a significant socioeconomic challenge. Stem cell therapies offer a promising avenue for intervention, primarily through mechanisms like telomere maintenance and cellular rejuvenation. However, conventional stem cell sources often come with limitations such as invasive collection, ethical concerns, safety risks, and high costs, which impede their clinical application. Urine-derived stem cells (USCs), in contrast, present an appealing alternative for regenerative medicine. Uniquely, USCs contain two distinct populations: those with high telomerase activity (TA) and long telomeres, and those with low or undetectable TA. Notably, the unique presence of telomerase-active USCs provides a novel avenue for addressing telomere attrition, a primary hallmark of biological aging, and holds significant translational geroscience relevance. Unlike stem cells derived from bone marrow or adipose tissue, which lack TA, USCs are obtained non-invasively through routine urination, significantly reducing patient discomfort and ethical issues. Moreover, compared to induced pluripotent stem cells (iPSCs), USCs pose a lower risk of tumorigenicity and require less complex manipulation, simplifying their journey to clinical use. USCs demonstrate robust proliferative capacity, broad differentiation potential, and enhanced safety profiles, making them well-suited for addressing age-related tissue degeneration and functional decline. Preclinical studies have already shown their effectiveness in mitigating age-related disorders and facilitating personalized medicine through disease modeling and drug discovery. While USC-based therapies are still in early development, their unique properties—especially the presence of USCs with robust telomerase activity—position them as an accessible and promising platform for regenerative medicine to combat age-related decline.
{"title":"Telomerase-active urine-derived stem cells: Regenerative solutions for aging","authors":"Xi Cheng , Qiao-Yu Fu , Yun-Ling Zheng , Gennadiy P. Moiseyev , Fang-Chi Hsu , Jian-Xing Ma , Qing-Feng Li , Anthony Atala , Yuan-Yuan Zhang","doi":"10.1016/j.arr.2025.102939","DOIUrl":"10.1016/j.arr.2025.102939","url":null,"abstract":"<div><div>Aging is a complex process that leads to various pathologies and poses a significant socioeconomic challenge. Stem cell therapies offer a promising avenue for intervention, primarily through mechanisms like telomere maintenance and cellular rejuvenation. However, conventional stem cell sources often come with limitations such as invasive collection, ethical concerns, safety risks, and high costs, which impede their clinical application. Urine-derived stem cells (USCs), in contrast, present an appealing alternative for regenerative medicine. Uniquely, USCs contain two distinct populations: those with high telomerase activity (TA) and long telomeres, and those with low or undetectable TA. Notably, the unique presence of telomerase-active USCs provides a novel avenue for addressing telomere attrition, a primary hallmark of biological aging, and holds significant translational geroscience relevance. Unlike stem cells derived from bone marrow or adipose tissue, which lack TA, USCs are obtained non-invasively through routine urination, significantly reducing patient discomfort and ethical issues. Moreover, compared to induced pluripotent stem cells (iPSCs), USCs pose a lower risk of tumorigenicity and require less complex manipulation, simplifying their journey to clinical use. USCs demonstrate robust proliferative capacity, broad differentiation potential, and enhanced safety profiles, making them well-suited for addressing age-related tissue degeneration and functional decline. Preclinical studies have already shown their effectiveness in mitigating age-related disorders and facilitating personalized medicine through disease modeling and drug discovery. While USC-based therapies are still in early development, their unique properties—especially the presence of USCs with robust telomerase activity—position them as an accessible and promising platform for regenerative medicine to combat age-related decline.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102939"},"PeriodicalIF":12.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pancreatic beta cells are highly specialized cells that possess unique metabolic programs to ensure insulin secretion matches nutritional status for maintaining glucose homeostasis. However, in type 2 diabetes mellitus (T2DM), prolonged exposure to excessive nutrients (glucose, lipids) induces toxicity that leads to progressive beta cell failure and impaired insulin secretion, whose underlying mechanisms remain unclear. This review summarizes the distinctive metabolic features of pancreatic beta cells under physiological conditions and the mechanisms of glucolipotoxicity-driven metabolic reprogramming in pathological states (T2DM). Under chronic nutrient overload, beta cells undergo dynamic metabolic remodeling, resulting in the loss of characteristic metabolic programs and triggering interconnected stress damage networks including inflammation, oxidative stress, and endoplasmic reticulum stress. Meanwhile, disrupted transcriptional programs under metabolic stress also lead to the loss of beta cell identity. In response, beta cells attempt to evolve unique carbon flux metabolic reprogramming mechanisms to achieve fuel “detoxification.” These processes are critical for identifying key nodes in beta cell metabolic reprogramming. Finally, the review outlines therapeutic strategies targeting beta cell metabolic reprogramming, particularly emerging approaches focusing on microRNAs and restoring beta cell identity and function. This article aims to delineate the key nodes in the transition of beta cells from physiological to pathological metabolic states, providing a theoretical basis for identifying reversible stages in disease progression and restoring metabolic flexibility to achieve beta cell functional protection.
{"title":"Metabolic reprogramming of pancreatic beta cells in type 2 diabetes and its therapeutic strategy","authors":"Linxuan Miao , Runyu Miao , Yiqi Yao , Xinyi Fang , Huifang Guan , Jiaxing Tian , Xiaolin Tong","doi":"10.1016/j.arr.2025.102938","DOIUrl":"10.1016/j.arr.2025.102938","url":null,"abstract":"<div><div>Pancreatic beta cells are highly specialized cells that possess unique metabolic programs to ensure insulin secretion matches nutritional status for maintaining glucose homeostasis. However, in type 2 diabetes mellitus (T2DM), prolonged exposure to excessive nutrients (glucose, lipids) induces toxicity that leads to progressive beta cell failure and impaired insulin secretion, whose underlying mechanisms remain unclear. This review summarizes the distinctive metabolic features of pancreatic beta cells under physiological conditions and the mechanisms of glucolipotoxicity-driven metabolic reprogramming in pathological states (T2DM). Under chronic nutrient overload, beta cells undergo dynamic metabolic remodeling, resulting in the loss of characteristic metabolic programs and triggering interconnected stress damage networks including inflammation, oxidative stress, and endoplasmic reticulum stress. Meanwhile, disrupted transcriptional programs under metabolic stress also lead to the loss of beta cell identity. In response, beta cells attempt to evolve unique carbon flux metabolic reprogramming mechanisms to achieve fuel “detoxification.” These processes are critical for identifying key nodes in beta cell metabolic reprogramming. Finally, the review outlines therapeutic strategies targeting beta cell metabolic reprogramming, particularly emerging approaches focusing on microRNAs and restoring beta cell identity and function. This article aims to delineate the key nodes in the transition of beta cells from physiological to pathological metabolic states, providing a theoretical basis for identifying reversible stages in disease progression and restoring metabolic flexibility to achieve beta cell functional protection.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"113 ","pages":"Article 102938"},"PeriodicalIF":12.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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