Aging and Disease最新文献

{"title":"Crossing Pathological Boundaries: Multi-Target Restoration of the Neurovascular Unit in Alzheimer's and Vascular Dementia-From Modern Therapeutics to Traditional Chinese Medicine.","authors":"Tengyu Zhao, Pengyu Pan, Ying Jia, Yuhan Zhou, Xinyue Zhang, Huibo Guan, Quan Li, Yanyan Zhou","doi":"10.14336/AD.2025.0801","DOIUrl":"https://doi.org/10.14336/AD.2025.0801","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and vascular dementia (VD) are the two most common forms of dementia, and they share common mechanisms, especially in regard to neurovascular dysfunction. There has been increasing evidence that the disruption of the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, neurons, and basement membrane, is one of the key early events in both AD and VD. The objective of this review is to summarize the structure and physiological function of the NVU, then discuss the pathological remodeling of the NVU in AD and VD and finally, show emerging evidence of multi-target approaches that restore the NVU and neurovascular protection. We begin with a description of the structure, and dietary regulatory roles of the NVU in cerebral homeostasis, especially related to Aβ, the blood-brain barrier (BBB), and neurovascular coupling (NVC). The NVU is then related to the pathological events that cause AD and VD, specifically to impaired Aβ clearance, inflammatory cascades, oxidative stress, and neurovascular uncoupling. Finally, the discussion focuses on a multi-target approach involving exercise, estrogen therapy, mesenchymal stem cells/exosomes, remote ischemic conditioning (RIC), and mindfulness meditation, and analyzes its implications for recovering NVU structure and function. We also discuss the concept of traditional Chinese medicine (TCM) approaches associated with NVU modulation with herbal formulas, traditional Chinese exercises and acupuncture, which has integrative pathways for MVU modulation. NVU dysfunction has a significant and converging impact on the development of both AD and VD. There is considerable support for multi-pathway neurovascular unit targeting, which should show a significant delay in cognitive decline. Incorporating multi-modal evidence from contemporary and traditional medical systems could offer new insights for individualized, neurovascular-targeted therapy for dementia.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Risk Prediction Model for Stroke-Heart Syndrome Following Endovascular Therapy.","authors":"Lanjing Wang, Shuangfeng Huang, Yongle Wang, Omar Elmadhoun, Changhong Ren, Wenbo Zhao, Yao Yu, Guiyou Liu, Xunming Ji, Sijie Li","doi":"10.14336/AD.2025.10710","DOIUrl":"https://doi.org/10.14336/AD.2025.10710","url":null,"abstract":"<p><p>Stroke-heart syndrome (SHS) significantly impacts patient prognosis, and reperfusion treatment strategies may have an impact on the occurrence of SHS following acute ischemic stroke (AIS). This study aimed to develop a nomogram-based SHS prediction model for anterior circulation stroke patients after endovascular therapy (EVT), addressing the current gap in early risk stratification of this population. This retrospective study enrolled 218 AIS patients who underwent EVT between January 2013 and June 2021, with an observed SHS incidence of 13.8% within the first two weeks post-EVT. We used the least absolute shrinkage and selection operator regression and multivariate logistic regression analysis to identify variables strongly associated with SHS. The results showed that age (OR 1.060, 95% CI 1.021-1.100, P = 0.002), hyperlipidemia (OR 3.400, 95% CI 1.289-8.968, P = 0.013), creatinine (OR 1.023, 95% CI 1.000-1.046, P = 0.049), and total anterior circulation infarct (TACI, OR 4.875, 95% CI 1.984-11.980, P = 0.001) were significantly associated with SHS and were subsequently incorporated into the construction of a nomogram-based prediction model. The area under receiver-operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow test, and Brier score were employed to comprehensively assess the accuracy and calibration of this model. The results demonstrate that the model exhibits good discriminatory ability (AUC = 0.812), calibration (Hosmer-Lemeshow test P = 0.855, Brier score = 0.098), and robustness (internal cross-validation AUC = 0.811). Furthermore, we assessed neurological outcomes at 3 months post-stroke using the modified Rankin Scale and found that SHS was independently associated with an increased risk of unfavorable functional outcome (OR 3.267, 95% CI 1.159-9.212, P = 0.025). In conclusion, SHS significantly increases the risk of unfavorable outcomes in AIS patients undergoing EVT. The nomogram, incorporating age, hyperlipidemia, TACI, and creatinine, exhibits strong predictive accuracy for early SHS; nevertheless, multicenter prospective validation is warranted prior to clinical implementation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between Brain Natriuretic Peptide and QTc Prolongation on Mortality in Patients with Stroke-Heart Syndrome.","authors":"Yongle Wang, Mingyi He, Lanjing Wang, Omar Elmadhoun, Fangyan Liu, Wenbo Zhao, Changhong Ren, Yuchuan Ding, Xunming Ji, Sijie Li","doi":"10.14336/AD.2025.10711","DOIUrl":"https://doi.org/10.14336/AD.2025.10711","url":null,"abstract":"<p><p>Stroke-heart syndrome (SHS) is associated with early mortality in patients with acute ischemic stroke (AIS). However, reliable methods for timely risk stratification remain elusive. Combined monitoring of neurohormonal activation and electrocardiography may help identifying early mortality risk in SHS patients. This study investigates the interaction between elevated BNP and QTc prolongation on short-term mortality in SHS patients. This cohort study included patients with suspected AIS and concomitant SHS. SHS is defined as new-onset cardiac dysfunction after AIS, including acute coronary syndrome, heart failure, and arrhythmias. All patients underwent laboratory tests and electrocardiographic evaluations. Prolonged QTc was defined as &;gt430 milliseconds (ms) in males and &;gt450 ms in females. Patients were followed up for three months, and the study outcomes were all-cause mortality and cardiovascular and cerebrovascular disease (CCVD) mortality. Cox regression models were used to assess the relationship between BNP, QTc interval, and mortality, and the interaction between BNP and the QTc interval on mortality was analyzed. A total of 448 patients were enrolled in this analysis. Prolonged QTc was present in 217 patients (48.44%). Elevated BNP was associated with prolonged QTc (OR 1.90; 95% CI, 1.20-3.01, p=0.006). Elevated BNP, but not prolonged QTc, increased the risk of all-cause and CCVD mortality (HR 5.94; 95% CI, 1.22-29.03, p=0.028 and HR 5.48; 95% CI, 1.01-29.70, p=0.048, respectively). There was a significant interaction between elevated BNP and prolonged QTc on all-cause mortality (p for interaction &;lt0.001). Patients with prolonged QTc and higher BNP had highest risk of all-cause mortality (HR 4.92, 95% CI, 1.03-23.39, p=0.045). This study highlights a significant interaction between prolonged QTc and elevated BNP levels in predicting short-term all-cause mortality among AIS patients with SHS. Prolonged QTc emerges as a critical marker of increased mortality risk, particularly in patients with elevated BNP levels.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD.","authors":"Milad Shademan, Sarah Flannery, Erik Bos, Tom M J Evers, Vahid Sheikhhassani, Alireza Mashaghi, Benno Kusters, Baziel van Engelen, Thom T Sharp, Roman Fischer, Benedikt M Kessler, Vered Raz","doi":"10.14336/AD.2025.0699","DOIUrl":"https://doi.org/10.14336/AD.2025.0699","url":null,"abstract":"<p><p>Aggregation of RNA-binding proteins (RBPs) is a hallmark of several age-related neuromuscular diseases. However, our understanding of how these aggregates drive dysfunction is often limited by the use of non-disease-relevant models. Oculopharyngeal muscular dystrophy (OPMD) is caused by a short alanine expansion mutation in the PABPN1 gene, which leads to nuclear aggregation of the protein. To investigate how these aggregates impair muscle cell function, we developed a muscle cell model with inducible expression of the pathogenic PABPN1 (A16) variant and confirmed its relevance to OPMD. Using subcellular fractionation combined with mass spectrometry and RNA sequencing, we examined the molecular consequences of nuclear PABPN1 aggregation. In the cytoplasmic fraction, we observed significant impairments in cellular metabolism and biomechanics. In the nuclear fraction, RNA metabolism was broadly disrupted, and additional RBPs were significantly enriched in insoluble aggregates. Importantly, mRNAs trapped within the aggregates were associated with impaired nuclear export and decreased translation efficiency, and the pathogenic PABPN1 variant led to reduced endogenous PABPN1 levels. Our findings support a model in which OPMD pathology arises from reduced levels of soluble PABPN1 due to nuclear aggregation and establish a mechanistic link between RBP aggregation and muscle cell dysfunction, highlighting shared pathological pathways across neuromuscular and neurodegenerative diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Trait Meta-Analysis Reveals a Genetic Link between Inflammation and Aging in Giant Cell Arteritis.","authors":"Laura Martínez-Gutiérrez, Inmaculada Rodriguez-Martin, Gonzalo Borrego-Yaniz, Martin Kerick, Carlo Salvarani, José Hernández-Rodríguez, María Cinta Cid, Miguel Ángel González-Gay, Ann W Morgan, Javier Martín, Lourdes Ortiz-Fernández, Ana Márquez","doi":"10.14336/AD.2025.0609","DOIUrl":"https://doi.org/10.14336/AD.2025.0609","url":null,"abstract":"<p><p>Giant cell arteritis (GCA) is a complex inflammatory disease affecting individuals over 50 suggesting a strong link with aging-related immune and vascular changes. However, the precise mechanisms underlying this age-related susceptibility remain poorly understood. Considering the relevance of aging in GCA, genetic factors influencing biological aging markers, such as telomere shortening and epigenetic age acceleration (EAA), might also contribute to its development. This study investigated the shared genetic basis between GCA and these markers to enhance understanding of the role of aging in this vasculitis. Data from approximately 6.6 million variants obtained from previously published genome-wide association studies (GWASs) of GCA (3,498 cases and 15,550 controls), telomere length (472,174 individuals), and EAA (34,710 individuals) were meta-analysed using ASSET. Significant variants (p<5×10^-8) were functionally annotated, and causal genes were prioritized using FUMA. Potential therapeutic candidates were identified through drug repurposing. This study identified 21 genetic variants shared between GCA and at least one aging marker. Two pleiotropic signals were annotated at PTPN22 and PLG, known risk factors for GCA, whereas the remainder represent potentially new susceptibility loci for this vasculitis. Several prioritized causal genes, such as SERPING1, SAR1B, SESN1, and SMC4, are involved in both inflammation and senescence, shedding light on the molecular pathways linking aging and GCA. Interestingly, expression levels of some of the prioritized genes PDE1B, ATXN2, and CNEP1R1, were dysregulated in immune cells from active patients. Drug repurposing analysis highlighted promising therapeutic candidates for GCA, including sulfasalazine, an anti-inflammatory agent, and investigational drugs targeting inflammatory pathways like NF-κB. These findings uncover significant genetic overlap between GCA and aging markers, offering insights into shared molecular pathways and potential new therapies targeting both inflammation and cellular senescence.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related Vascular Alterations in the Choroid Plexus: Novel Insights from Pathophysiology and Imaging Studies.","authors":"Zhe Sun, Chenyang Li, Dominique Leitner, Michelle Wu, Jiangyang Zhang, Thomas Wisniewski, Yulin Ge","doi":"10.14336/AD.2025.0735","DOIUrl":"https://doi.org/10.14336/AD.2025.0735","url":null,"abstract":"<p><p>The choroid plexus (ChP), a highly vascularized brain structure responsible for cerebrospinal fluid (CSF) production, undergoes significant age-related changes that may contribute to neurodegenerative diseases involving disrupted immune regulation, fluid homeostasis and waste clearance. Compared to other brain regions, vascular research on the ChP remains limited despite its critical role as a central interface between the blood and CSF. This review focuses on age-related vascular and structural alterations in the ChP from both histopathological and neuroimaging perspectives, and explores their impact on CSF dynamics, immune regulation, and the integrity of the blood-CSF barrier (BCSFB). Rather than shrinking, the aging ChP often enlarges due to dystrophic changes, as shown in volumetric MRI studies. Histological studies reveal epithelial degeneration, basement membrane thickening, and stromal fibrosis in the normal aging process. In dementia such as Alzheimer's disease (AD), proteomic studies have identified upregulation of AD- and immune-related proteins, along with downregulation of proteins linked to CSF clearance and metabolic support. Emerging high-resolution contrast-enhanced MRI techniques now allow in vivo visualization of microvascular changes within the ChP, shedding light on its normal and abnormal aging processes. Understanding these alterations is critical, as they may influence the onset and progression of various neurological diseases such as AD, Parkinson's disease (PD), normal pressure hydrocephalus, and amyotrophic lateral sclerosis (ALS). The recent advancements and challenges described in this study underscore the need for deeper investigation into ChP aging to inform future diagnostic and therapeutic strategies of neurodegenerative diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen-Specifically Activated CD8+ and Double-Negative T Cells Accumulate in the Brain of Alzheimer's Disease Mice.","authors":"Juliane Gellrich, Johanna Ruhnau, Lea Köslich, Stefan Gross, Agnes Flöel, Juliane Schulze, Antje Vogelgesang","doi":"10.14336/AD.2025.0452","DOIUrl":"https://doi.org/10.14336/AD.2025.0452","url":null,"abstract":"<p><p>Emerging evidence suggests adaptive immunity plays a key role in cognitive function and neurodegenerative diseases. However, the specific contribution of T cells in Alzheimer's disease (AD) remains poorly understood. Despite successful T cell modulation in other neurological conditions, similar strategies in AD remain underexplored due to gaps in our understanding of antigen-specific T cell activity and antigen-unspecific bystander activation in the diseased brain. In this study, we used flow cytometry to characterize T cell populations and their activation mode in an AD mouse model. By assessing GFP expression in C57BL/6J-Tg(Nr4a1-EGFP/cre)820Khog; Tg(APPswe,PSEN1dE9)85Dbo/Mmjax mice, we distinguished antigen-dependent from antigen-independent activation in CD4⁺, CD8⁺, and double-negative T cells (DNTs). This approach allows analysis of the full repertoire of antigen-specifically activated T cells in a physiological immune system without prior knowledge of target antigens. AD-like amyloid pathology progression was monitored by monthly scoring until mice reached 2, 6, 10-12 or 15-18 months of age and Aβ-quantification via thioflavine S staining. Antigen-specific activation during AD development was assessed by comparing AD mice with wild-type littermates. At 15-18 months, AD mice exhibited elevated numbers of activated, highly differentiated DNTs, along with increased antigen-specific CD8⁺ and DNT cells relative to controls. These results indicate a significant role for antigen-dependent immune activity in AD, highlighting CD8⁺ T cells and DNTs as potential therapeutic targets.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Clocks Identify Harmful Epigenetic Aging Linked to Depression Severity and Cognitive Deficits in Major Depressive Disorder.","authors":"Chao Liufu, Tao Pang, Haohao Zheng, Lei Yang, Li Yang, Xuebing Huang, Ying Qian, Suhua Chang","doi":"10.14336/AD.2025.0781","DOIUrl":"https://doi.org/10.14336/AD.2025.0781","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a prevalent mental illness characterized by significant morbidity and mortality. Cognitive impairment is a common feature of MDD, closely related to the aging process. Epigenetic aging calculated using DNA methylation is an important marker of biological aging. This study aims to investigate the relationships among MDD, epigenetic aging, and cognitive function. We assessed age acceleration using epigenetic clocks based on DNA methylation data in discovery dataset with 39 MDD patients and 40 healthy controls, and then validated the results in one independent MDD cohort with 359 cases and 68 controls. The results revealed that patients with MDD exhibited significantly greater age acceleration as measured by the DamAge clock and elevated mortality risk as indicated by the Zhang clock. Notably, the age acceleration of DamAge was positively correlated with depressive symptom severity. Epigenome-wide association study of the age acceleration of DamAge identified 1,472 significant CpG sites. Enrichment analyses further revealed that these CpG sites are potentially involved in cytoskeletal mechanisms, signaling pathways, and inflammatory response. Cognitive assessments showed significant correlations between emotion recognition task performance and age acceleration from multiple epigenetic clocks, suggesting a link between accelerated epigenetic aging and cognitive impairment in MDD. Our results underscore the potential role of epigenetic aging in understanding the biological underpinnings of MDD and its associated cognitive dysfunctions.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decentralizing Pulmonary Screening for China's Aging Population: From Hospitals to Communities.","authors":"Leiwen Fu, Wei Shu, Yuxian Sun, Liang Li, Jian Du","doi":"10.14336/AD.2025.1027","DOIUrl":"https://doi.org/10.14336/AD.2025.1027","url":null,"abstract":"<p><p>China's aging population faces a growing burden of chronic respiratory diseases, straining the public health system. Despite the Healthy China 2030 plan's emphasis on prevention and early detection, systemic barriers, such as low public awareness, urban-rural disparities, fragmented screening models, and uneven specialist distribution, hinder effective pulmonary care for older adults. To address these challenges, a shift toward community-based strategies, including mobile low-dose CT (LDCT) screening units, is proposed. These units improve accessibility, especially in rural areas, while AI integration enhances diagnostic accuracy and telemedicine bridges specialist gaps. Strengthening local healthcare capacity through training, policy support, and coordinated care among community health stations, hospitals, and the CDC is critical. Community engagement further boosts participation and follow-up. Success will be measured by early diagnosis rates, reduced disparities, and cost-effectiveness. Aligning with Healthy China 2030, this integrated approach promises equitable, sustainable respiratory care for aging populations.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and Pathogenesis of Diabetic Cognitive Impairment: A Comprehensive Review.","authors":"Change Qi, Ming Qin, Yu Wang, Cong Li, Huiying Yan, Lina Feng, Mingquan Li","doi":"10.14336/AD.2025.0769","DOIUrl":"https://doi.org/10.14336/AD.2025.0769","url":null,"abstract":"<p><p>Diabetic cognitive impairment (DCI) is a form of cognitive dysfunction that affects individuals with diabetes, marking it as one of the complications linked to this disease. This condition typically presents as deficits in various cognitive abilities, such as memory, learning, language, motor skills, perception, and attention. Studies show that around 13% of diabetic individuals aged 65 to 74 experience cognitive impairment, with this figure rising to 24% for those over 75. As the global incidence of DCI increases, the economic and caregiving challenges for both individuals and society are also growing. The specific mechanisms underlying DCI remain unclear, and the relationships among various pathological processes are still under investigation. The study of DCI mechanisms continues to present numerous unresolved mysteries, such as unclear causal relationships: does metabolic disorder (e.g., hyperglycemia) directly damage neurons, or does it indirectly affect cognition through vascular lesions? Additionally, the mechanisms of individual heterogeneity pose further questions: why do some diabetic patients experience cognitive decline (CD) while others do not? Therefore, understanding the pathological alterations and the fundamental reason behind DCI is essential for improving early prevention and treatment strategies for individuals exhibiting clinical symptoms of this disorder. Furthermore, DCI represents a significant intersection between metabolic and neurodegenerative diseases, which encourages the integration of cognitive assessments into routine diabetes management. This article not only provides a systematic review of existing research but also serves as a bridge connecting basic science with clinical practice, offering theoretical support for the precise prevention and early diagnosis of DCI in patients.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}