Pub Date : 2024-09-26DOI: 10.1016/j.arr.2024.102512
Kamil Pabis , Diogo Barardo , Jan Gruber , Olga Sirbu , Marco Malavolta , Kumar Selvarajoo , Matt Kaeberlein , Brian K. Kennedy
Although lifespan extension remains the gold standard for assessing interventions proposed to impact the biology of aging, there are important limitations to this approach. Our reanalysis of lifespan studies from multiple sources suggests that short lifespans in the control group exaggerate the relative efficacy of putative longevity interventions. Results may be exaggerated due to statistical effects (e.g. regression to the mean) or other factors. Moreover, due to the high cost and long timeframes of mouse studies, it is rare that a particular longevity intervention will be independently replicated by multiple groups. To facilitate identification of successful interventions, we propose an alternative approach particularly suitable for well-characterized inbred and HET3 mice. In our opinion, the level of confidence we can have in an intervention is proportional to the degree of lifespan extension above the strain- and species-specific upper limit of lifespan, which we can estimate from comparison to historical controls. In the absence of independent replication, a putative mouse longevity intervention should only be considered with high confidence when control median lifespans are close to 900 days or if the final lifespan of the treated group is considerably above 900 days. Using this “900-day rule” we identified several candidate interventions from the literature that merit follow-up studies.
{"title":"The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience – Through the lens of the “900-day rule”","authors":"Kamil Pabis , Diogo Barardo , Jan Gruber , Olga Sirbu , Marco Malavolta , Kumar Selvarajoo , Matt Kaeberlein , Brian K. Kennedy","doi":"10.1016/j.arr.2024.102512","DOIUrl":"10.1016/j.arr.2024.102512","url":null,"abstract":"<div><div>Although lifespan extension remains the gold standard for assessing interventions proposed to impact the biology of aging, there are important limitations to this approach. Our reanalysis of lifespan studies from multiple sources suggests that short lifespans in the control group exaggerate the relative efficacy of putative longevity interventions. Results may be exaggerated due to statistical effects (e.g. regression to the mean) or other factors. Moreover, due to the high cost and long timeframes of mouse studies, it is rare that a particular longevity intervention will be independently replicated by multiple groups. To facilitate identification of successful interventions, we propose an alternative approach particularly suitable for well-characterized inbred and HET3 mice. In our opinion, the level of confidence we can have in an intervention is proportional to the degree of lifespan extension above the strain- and species-specific upper limit of lifespan, which we can estimate from comparison to historical controls. In the absence of independent replication, a putative mouse longevity intervention should only be considered with high confidence when control median lifespans are close to 900 days or if the final lifespan of the treated group is considerably above 900 days. Using this “900-day rule” we identified several candidate interventions from the literature that merit follow-up studies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102512"},"PeriodicalIF":12.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334149","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 : 2024-09-26DOI: 10.1016/j.arr.2024.102516
Xiaonan Hao, Huijing Zhang, Xinyi Zhao, Xin Peng, Kun Li
Background
The outcomes of older patients are significantly limited by hospitalization-associated disability (HAD), and there are currently few available management options for HAD. This review aimed to identify and quantify the risk factors for HAD, to provide reliable evidence for developing a HAD prevention program centered on risk factor management among older patients.
Methods
The MEDLINE, Embase, PsycINFO, CINAHL, and PubMed databases were searched in March 2024 to identify cross-sectional and cohort studies that used multivariable analysis to examine risk factors for HAD among older patients.
Results
We screened 883 studies, 21 of which met our inclusion criteria. Our findings revealed a substantial association between various risk factors and HAD among older patients. Specifically, advanced age, female sex, Caucasian ethnicity, comorbidity burden, better activities of daily living at admission, dementia diagnosis, and longer lengths of stay were significant risk factors for HAD. Furthermore, frailty, poor physical function, immobility, and delirium were identified as confirmed risk factors for HAD among older patients.
Conclusions
This review provided a comprehensive synthesis of available evidence on risk factors for HAD among older patients, serving as a valuable guide for the development of HAD prevention strategies both prior to and during hospitalization.
背景：住院相关残疾（HAD）严重限制了老年患者的治疗效果，而目前针对 HAD 的可用管理方案却很少。本综述旨在确定和量化 HAD 的风险因素，为制定以老年患者风险因素管理为中心的 HAD 预防计划提供可靠证据：方法：在 2024 年 3 月对 MEDLINE、Embase、PsycINFO、CINAHL 和 PubMed 数据库进行了检索，以确定使用多变量分析来研究老年患者 HAD 危险因素的横断面和队列研究：我们筛选了 883 项研究，其中 21 项符合纳入标准。我们的研究结果表明，在老年患者中，各种风险因素与 HAD 之间存在着很大的关联。具体来说，高龄、女性、白种人、合并症负担、入院时日常生活活动能力较强、痴呆诊断和住院时间较长是导致 HAD 的重要风险因素。此外，虚弱、身体功能差、行动不便和谵妄也被确认为老年患者发生 HAD 的风险因素：本综述全面综述了老年患者发生 HAD 的风险因素，为制定住院前和住院期间的 HAD 预防策略提供了宝贵的指导。
{"title":"Risk factors for hospitalization-associated disability among older patients: A systematic review and meta-analysis","authors":"Xiaonan Hao, Huijing Zhang, Xinyi Zhao, Xin Peng, Kun Li","doi":"10.1016/j.arr.2024.102516","DOIUrl":"10.1016/j.arr.2024.102516","url":null,"abstract":"<div><h3>Background</h3><div>The outcomes of older patients are significantly limited by hospitalization-associated disability (HAD), and there are currently few available management options for HAD. This review aimed to identify and quantify the risk factors for HAD, to provide reliable evidence for developing a HAD prevention program centered on risk factor management among older patients.</div></div><div><h3>Methods</h3><div>The MEDLINE, Embase, PsycINFO, CINAHL, and PubMed databases were searched in March 2024 to identify cross-sectional and cohort studies that used multivariable analysis to examine risk factors for HAD among older patients.</div></div><div><h3>Results</h3><div>We screened 883 studies, 21 of which met our inclusion criteria. Our findings revealed a substantial association between various risk factors and HAD among older patients. Specifically, advanced age, female sex, Caucasian ethnicity, comorbidity burden, better activities of daily living at admission, dementia diagnosis, and longer lengths of stay were significant risk factors for HAD. Furthermore, frailty, poor physical function, immobility, and delirium were identified as confirmed risk factors for HAD among older patients.</div></div><div><h3>Conclusions</h3><div>This review provided a comprehensive synthesis of available evidence on risk factors for HAD among older patients, serving as a valuable guide for the development of HAD prevention strategies both prior to and during hospitalization.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102516"},"PeriodicalIF":12.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334148","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 : 2024-09-24DOI: 10.1016/j.arr.2024.102510
Ludmila Kucikova , Xiong Xiong , Patricia Reinecke , Jessica Madden , Elizabeth Jackson , Oliver Tappin , Weijie Huang , Maria-Eleni Dounavi , Li Su
In the last decade, extensive research has emerged into understanding the impact of risk factors for Alzheimer’s Disease (AD) on brain in pre-symptomatic stages. We investigated the neuroimaging correlates of the APOEe4 genetic risk factor for AD in young adulthood, its relationship with cognition, and potential effects of other variables on the findings. While conventional volumetric analyses revealed no consistent differences, more sophisticated analyses identified subtle structural differences between APOEe4 carriers and non-carriers. Findings from diffusion studies were limited, but functional studies demonstrated consistent alterations in connectivity and activity. The complex relationship between APOE genotype, neuroimaging variables, and cognition revealed no consensus on the directionality of findings. Methodological choices, including analytical approaches, sample size, and the influence of other genes, gender, and ethnicity, varied across studies, impacting comparability and generalizability. Recommendations for future research include multimodal and longitudinal imaging, standardisation of pipelines, advanced analytical techniques, and collaborative data pooling.
{"title":"The effects of APOEe4 allele on cerebral structure, function, and related interactions with cognition in young adults","authors":"Ludmila Kucikova , Xiong Xiong , Patricia Reinecke , Jessica Madden , Elizabeth Jackson , Oliver Tappin , Weijie Huang , Maria-Eleni Dounavi , Li Su","doi":"10.1016/j.arr.2024.102510","DOIUrl":"10.1016/j.arr.2024.102510","url":null,"abstract":"<div><div>In the last decade, extensive research has emerged into understanding the impact of risk factors for Alzheimer’s Disease (AD) on brain in pre-symptomatic stages. We investigated the neuroimaging correlates of the <em>APOEe4</em> genetic risk factor for AD in young adulthood, its relationship with cognition, and potential effects of other variables on the findings. While conventional volumetric analyses revealed no consistent differences, more sophisticated analyses identified subtle structural differences between <em>APOEe4</em> carriers and non-carriers. Findings from diffusion studies were limited, but functional studies demonstrated consistent alterations in connectivity and activity. The complex relationship between <em>APOE</em> genotype, neuroimaging variables, and cognition revealed no consensus on the directionality of findings. Methodological choices, including analytical approaches, sample size, and the influence of other genes, gender, and ethnicity, varied across studies, impacting comparability and generalizability. Recommendations for future research include multimodal and longitudinal imaging, standardisation of pipelines, advanced analytical techniques, and collaborative data pooling.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102510"},"PeriodicalIF":12.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
People with dementia have an increased risk of hospitalization and mortality due to infections. We aimed to explore decision-making processes and interventions for detecting and managing suspected infections in people with dementia and involved actors and determinants. We conducted a scoping review, searching CINAHL and PubMed, and synthesized data through mapping and narratively. We identified 22 studies, based mostly on nursing homes and US data. Decision-making processes included recognition of infections based on observations of early signs and symptoms, actions when suspecting infections, and proxy/family involvement. Interventions included antimicrobial stewardship and other decision-support tools. Determinants included healthcare staff perceptions, and other system/person-related factors. Healthcare staff were the main actors, proxy/family were mentioned scarcely, and people with dementia only once. Our findings show scarcity of evidence on people with dementia and outside of the nursing homes. We highlight knowledge gaps and inform research shaping interventions for improving infection detection and management.
{"title":"Detection and management of suspected infections in people with dementia – A scoping review of current practices","authors":"Mihaela Ivosevic , Gritt Overbeck , Anne Holm , Gunhild Waldemar , Janet Janbek","doi":"10.1016/j.arr.2024.102520","DOIUrl":"10.1016/j.arr.2024.102520","url":null,"abstract":"<div><div>People with dementia have an increased risk of hospitalization and mortality due to infections. We aimed to explore decision-making processes and interventions for detecting and managing suspected infections in people with dementia and involved actors and determinants. We conducted a scoping review, searching CINAHL and PubMed, and synthesized data through mapping and narratively. We identified 22 studies, based mostly on nursing homes and US data. Decision-making processes included recognition of infections based on observations of early signs and symptoms, actions when suspecting infections, and proxy/family involvement. Interventions included antimicrobial stewardship and other decision-support tools. Determinants included healthcare staff perceptions, and other system/person-related factors. Healthcare staff were the main actors, proxy/family were mentioned scarcely, and people with dementia only once. Our findings show scarcity of evidence on people with dementia and outside of the nursing homes. We highlight knowledge gaps and inform research shaping interventions for improving infection detection and management.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102520"},"PeriodicalIF":12.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.arr.2024.102517
Tong Lei , Xiaoshuang Zhang , Gaoshuang Fu , Shaohan Luo , Ziwei Zhao , Shiwen Deng , Caifeng Li , Zhao Cui , Junxian Cao , Peng Chen , Hongjun Yang
The prevalence of neurodegenerative diseases (NDs) is increasing rapidly as the aging population accelerates, and there are still no treatments to halt or reverse the progression of these diseases. While traditional 2D cultures and animal models fail to translate into effective therapies benefit patients, 3D cultured human brain organoids (hBOs) facilitate the use of non-invasive methods to capture patient data. The purpose of this study was to review the research and application of hBO in disease models and drug screening in NDs. The pluripotent stem cells are induced in multiple stages to form cerebral organoids, brain region-specific organoids and their derived brain cells, which exhibit complex brain-like structures and perform electrophysiological activities. The brain region-specific organoids and their derived neurons or glial cells contribute to the understanding of the pathogenesis of NDs and the efficient development of drugs, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Glial-rich brain organoids facilitate the study of glial function and neuroinflammation, including astrocytes, microglia, and oligodendrocytes. Further research on the maturation enhancement, vascularization and multi-organoid assembly of hBO will help to enhance the research and application of NDs cellular models.
{"title":"Advances in human cellular mechanistic understanding and drug discovery of brain organoids for neurodegenerative diseases","authors":"Tong Lei , Xiaoshuang Zhang , Gaoshuang Fu , Shaohan Luo , Ziwei Zhao , Shiwen Deng , Caifeng Li , Zhao Cui , Junxian Cao , Peng Chen , Hongjun Yang","doi":"10.1016/j.arr.2024.102517","DOIUrl":"10.1016/j.arr.2024.102517","url":null,"abstract":"<div><div>The prevalence of neurodegenerative diseases (NDs) is increasing rapidly as the aging population accelerates, and there are still no treatments to halt or reverse the progression of these diseases. While traditional 2D cultures and animal models fail to translate into effective therapies benefit patients, 3D cultured human brain organoids (hBOs) facilitate the use of non-invasive methods to capture patient data. The purpose of this study was to review the research and application of hBO in disease models and drug screening in NDs. The pluripotent stem cells are induced in multiple stages to form cerebral organoids, brain region-specific organoids and their derived brain cells, which exhibit complex brain-like structures and perform electrophysiological activities. The brain region-specific organoids and their derived neurons or glial cells contribute to the understanding of the pathogenesis of NDs and the efficient development of drugs, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Glial-rich brain organoids facilitate the study of glial function and neuroinflammation, including astrocytes, microglia, and oligodendrocytes. Further research on the maturation enhancement, vascularization and multi-organoid assembly of hBO will help to enhance the research and application of NDs cellular models.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102517"},"PeriodicalIF":12.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334143","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 : 2024-09-24DOI: 10.1016/j.arr.2024.102515
Nargis Bano , Sameera Khan , Shakir Ahamad , Jitendra Singh Kanshana , Nawab John Dar , Sumbul Khan , Aamir Nazir , Shahnawaz Ali Bhat
The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.
肠道微生物群（GM）与大脑功能（如情绪、行为和认知）之间的密切联系已得到充分证实。肠道-大脑轴是肠道和大脑之间独特的双向交流系统，其中肠道微生物在维持各种分子和细胞过程中发挥着至关重要的作用。转基因通过各种途径和过程与大脑相互作用，包括代谢产物、迷走神经、HPA 轴、内分泌系统和免疫系统，以维持大脑的平衡。转基因菌群失调或转基因失衡与多种神经系统疾病有关，包括焦虑症、抑郁症和阿尔茨海默病（AD）。相反，阿兹海默病是由小胶质细胞介导的神经炎症和神经变性引起的。此外，转基因及其产品也会影响小胶质细胞介导的神经炎症和神经变性。尽管有证据表明转基因菌群失调与渐冻症的进展有关，但转基因参与调节渐冻症中小胶质细胞介导的神经炎症的情况仍然难以捉摸。重要的是，破译转基因调节小胶质细胞依赖性神经炎症的机制可能有助于制定潜在的治疗策略来缓解 AD。在此，我们回顾了目前有关转基因菌群失调参与 AD 中小胶质细胞激活和神经炎症的证据。我们还讨论了转基因影响小胶质细胞功能的可能机制及其对治疗干预的影响。此外，我们还探讨了以微生物群为目标的干预措施的潜力，如益生元、益生菌、粪便微生物群移植等，以此作为一种新型治疗策略来缓解神经炎症和 AD 的进展。通过了解和探索肠脑轴，我们希望彻底改变神经退行性疾病的治疗方法，其中许多疾病都有一个共同的主题，即小胶质细胞介导的神经炎症和神经退行性疾病。
{"title":"Microglia and gut microbiota: A double-edged sword in Alzheimer's disease","authors":"Nargis Bano , Sameera Khan , Shakir Ahamad , Jitendra Singh Kanshana , Nawab John Dar , Sumbul Khan , Aamir Nazir , Shahnawaz Ali Bhat","doi":"10.1016/j.arr.2024.102515","DOIUrl":"10.1016/j.arr.2024.102515","url":null,"abstract":"<div><div>The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102515"},"PeriodicalIF":12.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334147","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 : 2024-09-22DOI: 10.1016/j.arr.2024.102514
Rafael Antônio Vicente Lacerda , Janaína Aparecida Favero Desio , Camila Marciele Kammers , Silvana Henkes , Monique Freitas de Sá , Everton Ferreira de Souza , Driele Martins da Silva , Camilla Teixeira Pinheiro Gusmão , Júlio César Claudino dos Santos
Substantial sleep impairment in patients with Alzheimer's disease (AD) is one of the emerging points for continued efforts to better understand the disease. Individuals without cognitive decline, an important marker of the clinical phase of AD, may show early alterations in the sleep-wake cycle. The objective of this critical narrative review is to explore the bidirectional pathophysiological correlation between sleep disturbances and Alzheimer’s Disease. Specifically, it examines how the disruption of sleep homeostasis in individuals without dementia could contribute to the pathogenesis of AD, and conversely, how neurodegeneration in individuals with Alzheimer’s Disease might lead to dysregulation of the sleep-wake cycle. Recent scientific results indicate that sleep disturbances, particularly those related to impaired glymphatic clearance, may act as an important mechanism associated with the genesis of Alzheimer’s Disease. Additionally, amyloid deposition and tau protein hyperphosphorylation, along with astrocytic hyperactivation, appear to trigger changes in neurotransmission dynamics in areas related to sleep, which may explain the onset of sleep disturbances in individuals with AD. Disruption of sleep homeostasis appears to be a modifiable risk factor in Alzheimer’s disease. Whenever possible, the use of non-pharmacological strategies becomes important in this context. From a different perspective, additional research is needed to understand and treat the dysfunction of the sleep-wake cycle in individuals already affected by AD. Early recognition and correction of sleep disturbances in this population could potentially mitigate the progression of dementia and improve the quality of life for those with AD.
阿尔茨海默氏症（AD）患者的严重睡眠障碍是继续努力更好地了解这种疾病的新要点之一。认知能力下降是阿尔茨海默病临床阶段的一个重要标志，而没有认知能力下降的患者可能会出现睡眠-觉醒周期的早期改变。本评论旨在探讨睡眠障碍与阿尔茨海默病之间的双向病理生理学关联。具体来说，它探讨了未患痴呆症的人的睡眠平衡被破坏是如何导致阿兹海默病发病的，反之，阿兹海默病患者的神经变性又是如何导致睡眠-觉醒周期失调的。最近的科学研究结果表明，睡眠障碍，尤其是与糖腺清除功能受损有关的睡眠障碍，可能是与阿尔茨海默病发病相关的一个重要机制。此外，淀粉样蛋白沉积和 tau 蛋白过度磷酸化以及星形胶质细胞过度激活似乎会引发与睡眠相关区域的神经传递动力学发生变化，这或许可以解释为什么 AD 患者会出现睡眠障碍。睡眠平衡的破坏似乎是阿尔茨海默病的一个可改变的危险因素。在这种情况下，尽可能使用非药物疗法就变得非常重要。从另一个角度来看，还需要进行更多的研究，以了解和治疗已受阿兹海默症影响的人的睡眠-觉醒周期功能障碍。及早发现并纠正这类人群的睡眠障碍，有可能缓解痴呆症的进展，并提高注意力缺失症患者的生活质量。
{"title":"Sleep disorders and risk of alzheimer's disease: A two-way road","authors":"Rafael Antônio Vicente Lacerda , Janaína Aparecida Favero Desio , Camila Marciele Kammers , Silvana Henkes , Monique Freitas de Sá , Everton Ferreira de Souza , Driele Martins da Silva , Camilla Teixeira Pinheiro Gusmão , Júlio César Claudino dos Santos","doi":"10.1016/j.arr.2024.102514","DOIUrl":"10.1016/j.arr.2024.102514","url":null,"abstract":"<div><div>Substantial sleep impairment in patients with Alzheimer's disease (AD) is one of the emerging points for continued efforts to better understand the disease. Individuals without cognitive decline, an important marker of the clinical phase of AD, may show early alterations in the sleep-wake cycle. The objective of this critical narrative review is to explore the bidirectional pathophysiological correlation between sleep disturbances and Alzheimer’s Disease. Specifically, it examines how the disruption of sleep homeostasis in individuals without dementia could contribute to the pathogenesis of AD, and conversely, how neurodegeneration in individuals with Alzheimer’s Disease might lead to dysregulation of the sleep-wake cycle. Recent scientific results indicate that sleep disturbances, particularly those related to impaired glymphatic clearance, may act as an important mechanism associated with the genesis of Alzheimer’s Disease. Additionally, amyloid deposition and tau protein hyperphosphorylation, along with astrocytic hyperactivation, appear to trigger changes in neurotransmission dynamics in areas related to sleep, which may explain the onset of sleep disturbances in individuals with AD. Disruption of sleep homeostasis appears to be a modifiable risk factor in Alzheimer’s disease. Whenever possible, the use of non-pharmacological strategies becomes important in this context. From a different perspective, additional research is needed to understand and treat the dysfunction of the sleep-wake cycle in individuals already affected by AD. Early recognition and correction of sleep disturbances in this population could potentially mitigate the progression of dementia and improve the quality of life for those with AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102514"},"PeriodicalIF":12.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334150","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 : 2024-09-21DOI: 10.1016/j.arr.2024.102513
Philipp Niklas Ostermann , Teresa Hope Evering
Depending on the population studied, HIV-1-related neurocognitive impairment is estimated to impact up to half the population of people living with HIV (PLWH) despite the availability of combination antiretroviral therapy (cART). Various factors contribute to this neurocognitive impairment, which complicates our understanding of the molecular mechanisms involved. Biological aging has been implicated as one factor possibly impacting the development and progression of HIV-1-related neurocognitive impairment. This is increasingly important as the life expectancy of PLWH with virologic suppression on cART is currently projected to be similar to that of individuals not living with HIV. Based on our increasing understanding of the biological aging process on a cellular level, we aim to dissect possible interactions of aging- and HIV-1 infection-induced effects and their role in neurocognitive decline. Thus, we begin by providing a brief overview of the clinical aspects of HIV-1-related neurocognitive impairment and review the accumulating evidence implicating aging in its development (Part I). We then discuss potential interactions between aging-associated pathways and HIV-1-induced effects at the molecular level (Part II).
{"title":"The impact of aging on HIV-1-related neurocognitive impairment","authors":"Philipp Niklas Ostermann , Teresa Hope Evering","doi":"10.1016/j.arr.2024.102513","DOIUrl":"10.1016/j.arr.2024.102513","url":null,"abstract":"<div><div>Depending on the population studied, HIV-1-related neurocognitive impairment is estimated to impact up to half the population of people living with HIV (PLWH) despite the availability of combination antiretroviral therapy (cART). Various factors contribute to this neurocognitive impairment, which complicates our understanding of the molecular mechanisms involved. Biological aging has been implicated as one factor possibly impacting the development and progression of HIV-1-related neurocognitive impairment. This is increasingly important as the life expectancy of PLWH with virologic suppression on cART is currently projected to be similar to that of individuals not living with HIV. Based on our increasing understanding of the biological aging process on a cellular level, we aim to dissect possible interactions of aging- and HIV-1 infection-induced effects and their role in neurocognitive decline. Thus, we begin by providing a brief overview of the clinical aspects of HIV-1-related neurocognitive impairment and review the accumulating evidence implicating aging in its development (<em>Part I</em>). We then discuss potential interactions between aging-associated pathways and HIV-1-induced effects at the molecular level (<em>Part II</em>).</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102513"},"PeriodicalIF":12.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303176","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 : 2024-09-21DOI: 10.1016/j.arr.2024.102505
Amin Ullah , Yongxiu Chen , Rajeev K. Singla , Dan Cao , Bairong Shen
Menopause is an age-related change that persists for around one-third of a woman's life. Menopause increases the risk of metabolic illnesses such as diabetes, osteoporosis (OP), and nonalcoholic fatty liver disease (NAFLD). Immune mediators (pro-inflammatory cytokines), such as interleukin-1 (IL-1), IL-6, IL-17, transforming growth factor (TGF), and tumor necrosis factor (TNF), exacerbate the challenges of a woman undergoing menopause by causing inflammation and contributing to the development of these metabolic diseases in postmenopausal women. Furthermore, studies have shown that anti-inflammatory cytokines such as interleukin-1 receptor antagonists (IL-1Ra), IL-2, and IL-10 have a double-edged effect on diabetes and OP. Likewise, several interferon (IFN) members are double-edged swords in the OP. Therefore, addressing these immune mediators precisely may be an approach to improving the health of postmenopausal women. Hence, considering the significant changes in these cytokines, the present review focuses on the latest findings concerning the molecular mechanisms by which pro- and anti-inflammatory cytokines (interleukins) impact postmenopausal women with diabetes, OP, and NAFLD.
Furthermore, we comprehensively discuss the therapeutic approaches that identify cytokines as therapeutic targets, such as hormonal therapy, physical activities, natural inhibitors (drugs), and others. Finally, this review aims to provide valuable insights into the role of cytokines in postmenopausal women's diabetes, OP, and NAFLD. Deeply investigating the mechanisms and therapeutic interventions involved will address the characteristics of immune mediators (cytokines) and improve the management of these illnesses, thereby enhancing the general quality of life and health of the corresponding populations of women.
更年期是一种与年龄有关的变化，持续时间约占女性一生的三分之一。更年期会增加患糖尿病、骨质疏松症（OP）和非酒精性脂肪肝（NAFLD）等代谢性疾病的风险。白细胞介素-1（IL-1）、IL-6、IL-17、转化生长因子（TGF）和肿瘤坏死因子（TNF）等免疫介质（促炎细胞因子）会引起炎症，导致绝经后妇女患上这些代谢性疾病，从而加剧绝经妇女面临的挑战。此外，研究表明，白细胞介素-1 受体拮抗剂（IL-1Ra）、IL-2 和 IL-10 等抗炎细胞因子对糖尿病和 OP 有双刃剑效应。同样，几种干扰素（IFN）也是影响 OP 的双刃剑。因此，精确处理这些免疫介质可能是改善绝经后妇女健康的一种方法。因此，考虑到这些细胞因子的重大变化，本综述将重点关注有关促炎和抗炎细胞因子（白细胞介素）对患有糖尿病、OP 和非酒精性脂肪肝的绝经后妇女的影响的分子机制的最新发现。此外，我们还全面讨论了将细胞因子确定为治疗靶点的治疗方法，如激素疗法、体育锻炼、天然抑制剂（药物）等。最后，本综述旨在为细胞因子在绝经后女性糖尿病、OP 和非酒精性脂肪肝中的作用提供有价值的见解。深入研究其中涉及的机制和治疗干预措施，将解决免疫介质（细胞因子）的特性问题，并改善对这些疾病的管理，从而提高相应妇女群体的总体生活质量和健康水平。
{"title":"Exploring cytokines dynamics: Uncovering therapeutic concepts for metabolic disorders in postmenopausal women- diabetes, metabolic bone diseases, and non-alcohol fatty liver disease","authors":"Amin Ullah , Yongxiu Chen , Rajeev K. Singla , Dan Cao , Bairong Shen","doi":"10.1016/j.arr.2024.102505","DOIUrl":"10.1016/j.arr.2024.102505","url":null,"abstract":"<div><div>Menopause is an age-related change that persists for around one-third of a woman's life. Menopause increases the risk of metabolic illnesses such as diabetes, osteoporosis (OP), and nonalcoholic fatty liver disease (NAFLD). Immune mediators (pro-inflammatory cytokines), such as interleukin-1 (IL-1), IL-6, IL-17, transforming growth factor (TGF), and tumor necrosis factor (TNF), exacerbate the challenges of a woman undergoing menopause by causing inflammation and contributing to the development of these metabolic diseases in postmenopausal women. Furthermore, studies have shown that anti-inflammatory cytokines such as interleukin-1 receptor antagonists (IL-1Ra), IL-2, and IL-10 have a double-edged effect on diabetes and OP. Likewise, several interferon (IFN) members are double-edged swords in the OP. Therefore, addressing these immune mediators precisely may be an approach to improving the health of postmenopausal women. Hence, considering the significant changes in these cytokines, the present review focuses on the latest findings concerning the molecular mechanisms by which pro- and anti-inflammatory cytokines (interleukins) impact postmenopausal women with diabetes, OP, and NAFLD.</div><div>Furthermore, we comprehensively discuss the therapeutic approaches that identify cytokines as therapeutic targets, such as hormonal therapy, physical activities, natural inhibitors (drugs), and others. Finally, this review aims to provide valuable insights into the role of cytokines in postmenopausal women's diabetes, OP, and NAFLD. Deeply investigating the mechanisms and therapeutic interventions involved will address the characteristics of immune mediators (cytokines) and improve the management of these illnesses, thereby enhancing the general quality of life and health of the corresponding populations of women.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102505"},"PeriodicalIF":12.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303172","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 : 2024-09-21DOI: 10.1016/j.arr.2024.102511
Nameerah Rakhe, Lokesh Kumar Bhatt
Valosin-containing protein (VCP), also known as p97, plays a crucial role in various cellular processes, including protein degradation, endoplasmic reticulum-associated degradation, and cell cycle regulation. While extensive research has been focused on VCP's involvement in protein homeostasis and its implications in neurodegenerative diseases, emerging evidence suggests a potential link between VCP and cardiovascular health. VCP is a key regulator of mitochondrial function, and its overexpression or mutations lead to pathogenic diseases and cellular stress responses. The present review explores VCP's roles in numerous cardiovascular disorders including myocardial ischemia/reperfusion injury, cardiac hypertrophy, and heart failure. The review dwells on the roles of VCP in modifying mitochondrial activity, promoting S-nitrosylation, regulating mTOR signalling and demonstrating cardioprotective effects. Further research into VCP might lead to novel interventions for cardiovascular disease, particularly those involving ischemia/reperfusion injury and hypertrophy.
{"title":"Valosin-containing protein: A potential therapeutic target for cardiovascular diseases","authors":"Nameerah Rakhe, Lokesh Kumar Bhatt","doi":"10.1016/j.arr.2024.102511","DOIUrl":"10.1016/j.arr.2024.102511","url":null,"abstract":"<div><div>Valosin-containing protein (VCP), also known as p97, plays a crucial role in various cellular processes, including protein degradation, endoplasmic reticulum-associated degradation, and cell cycle regulation. While extensive research has been focused on VCP's involvement in protein homeostasis and its implications in neurodegenerative diseases, emerging evidence suggests a potential link between VCP and cardiovascular health. VCP is a key regulator of mitochondrial function, and its overexpression or mutations lead to pathogenic diseases and cellular stress responses. The present review explores VCP's roles in numerous cardiovascular disorders including myocardial ischemia/reperfusion injury, cardiac hypertrophy, and heart failure. The review dwells on the roles of VCP in modifying mitochondrial activity, promoting S-nitrosylation, regulating mTOR signalling and demonstrating cardioprotective effects. Further research into VCP might lead to novel interventions for cardiovascular disease, particularly those involving ischemia/reperfusion injury and hypertrophy.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102511"},"PeriodicalIF":12.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309340","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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