Current Neuropharmacology最新文献

{"title":"Microbiota-Gut-Brain Axis in Mood and Neuropsychiatric Disorders: Therapeutic Opportunities: Mini-thematic Issue.","authors":"István Bókkon, Noémi Császár-Nagy","doi":"10.2174/011570159X535767260828094145","DOIUrl":"https://doi.org/10.2174/011570159X535767260828094145","url":null,"abstract":"","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944348","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":"Innovations in Nanotechnology-based Drug Delivery for Ischemic Stroke.","authors":"Sanjeev Nirala, Shuyu Wu, Ahmed Hammad, Chunming Huang, Qingchun Mu","doi":"10.2174/011570159X456462260824155900","DOIUrl":"https://doi.org/10.2174/011570159X456462260824155900","url":null,"abstract":"<p><strong>Background: </strong>The blood-brain barrier (BBB) blocks over 98% of neuroactive drugs from reaching the brain, constituting a major obstacle to effective treatment for ischemic stroke. Nanotechnology offers innovative solutions for overcoming this barrier; however, the field currently lacks a unified framework to guide the rational design of nanocarriers. This study aims to systematically evaluate nanotechnology-based drug delivery systems for ischemic stroke according to their underlying BBB transport mechanisms-namely, adsorption-mediated transport (AMT), receptor-mediated transport (RMT), and cell-mediated transport (CMT)-and to validate the hypothesis that CMT strategies are superior for targeted delivery to the ischemic hemisphere.</p><p><strong>Methods: </strong>In a murine MCAO model, targeted nanoparticles were employed alongside a non-targeted control for original validation (n = 3/group; 60-minute occlusion; 5 mg/kg intravenous dose). Outcomes included NIR-II fluorescence imaging (1-24 hours), T2-weighted MRI (72 hours), histology, immunofluorescence, TUNEL apoptosis assays, and RNA-seq transcriptomics.</p><p><strong>Results: </strong>Compared to the AMT/RMT methods, CMT-based strategies-exemplified by neutrophil \"hitchhiking\" (and neutrophil elastase inhibition -demonstrated superior accumulation within the ischemic hemisphere. Targeted Nano treatment achieved: (i) significantly enhanced cerebral fluorescence at 8 hours compared to non-targeted Nano treatment (ii) a reduction in infarct volume from (iii) reduced neutrophil infiltration and decreased apoptosis (iv) preservation of blood-brain barrier integrity and reduced Evans blue extravasation; (v) absence of acute organ toxicity; and (vi) normalization of transcriptomic pathways associated with inflammation (TNF, NF-κB, IL-17) and oxidative stress.</p><p><strong>Conclusion: </strong>Endogenous cell-mediated transport(CMT) represents a superior strategy for traversing the blood-brain barrier in ischemic stroke, enabling the attainment of therapeutic drug concentrations at the lesion site while simultaneously mitigating systemic toxicity. Neutrophil-targeted nanotherapy-whether achieved through drug-loaded nanoparticle \"hitchhiking\" or the inhibition of neutrophil elastase-offers a paradigm-shifting approach to the treatment of acute ischemic stroke.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944299","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":"Integrated Bioinformatics Analysis Investigating the Potential Role and Mechanism of INS in Cocaine-Induced Stroke.","authors":"Zeyu Han, Chunyu Wang, Tian Fu, Gaoyan Wang","doi":"10.2174/011570159X485765260820081251","DOIUrl":"https://doi.org/10.2174/011570159X485765260820081251","url":null,"abstract":"<p><strong>Background: </strong>Cocaine abuse is associated with an increased risk of stroke, yet the underlying molecular mechanisms remain poorly understood.</p><p><strong>Methods: </strong>An integrated framework combining network toxicology, machine learning, Mendelian randomization (MR), single-cell RNA sequencing (scRNA-seq), virtual knockout, molecular docking, and molecular dynamics (MD) simulations was applied to identify and validate key molecular links between cocaine exposure and stroke.</p><p><strong>Results: </strong>A total of 319 shared targets were identified, from which three core genes (TNF, INS, CDC42) were screened. MR analysis demonstrated a potential causal association between INS and stroke. scRNA-seq showed high expression of Ins2 (murine homolog of human INS) in epithelial cells, with extensive intercellular communication between epithelial and endothelial cells. Additionally, 196 genes exhibited significant changes following virtual knockout of Ins2, which were enriched in neurogenic and metabolic pathways. Molecular docking and MD simulations confirmed stable binding between cocaine and INS.</p><p><strong>Discussion: </strong>Mechanistically, cocaine-induced stroke is mediated by a mutually reinforcing pathological network forming a \"mitochondrial damage-oxidative stress-inflammation-coagulation\" vicious cycle, wherein cocaine crosses the blood-brain barrier to disrupt cerebral vasculature function, activate platelets, and trigger proinflammatory responses. INS, identified as a candidate gene via MR analysis (overcoming confounding biases of observational studies), is specifically highly expressed in choroid plexus epithelial cells (CPECs) and forms a choroid plexus-insulin signaling axis that regulates cerebral energy metabolism, oxidative stress, inflammation, and neurovascular homeostasis via cerebrospinal fluid. Virtual knockout of Ins2 perturbed pathways linked to energy metabolism disorder and neural repair, confirming its pivotal role in maintaining cerebral homeostasis, while stable cocaine-INS binding suggests cocaine may interfere with this protective axis.</p><p><strong>Conclusion: </strong>INS may serve as a potential key regulatory factor linking cocaine exposure with stroke risk. This study provides novel mechanistic insights and a systematic analytical framework for investigating drug-induced cerebrovascular diseases.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944311","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":"Artemisinin Activates AMPK to Rescue Neuronal Cells and 3xTg Mice from Aβ1-42 Neurotoxicity.","authors":"Yitian Chen, Wenjun Xiong, Lijun Ge, Wenhua Zheng","doi":"10.2174/011570159X504863260824051801","DOIUrl":"https://doi.org/10.2174/011570159X504863260824051801","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a multifactorial etiology, including amyloid β1-42 (Aβ1-42) accumulation, oxidative stress, tau hyperphosphorylation, and neuroinflammation. Among these pathological processes, redox imbalance and inflammation are key drivers of neuronal injury and are closely linked to dysregulation of AMPK signaling. Artemisinin (ART), a clinically safe antimalarial sesquiterpene lactone, has emerged as a promising neuroprotective candidate due to its antioxidant and anti-inflammatory properties. However, its role in modulating AMP-activated protein kinase (AMPK)-dependent neuroprotection in AD remains to be fully elucidated. Given that AMPK is a master regulator of cellular energy homeostasis, oxidative stress mitigation, and neuronal survival, and that its progressive dysregulation heavily accelerates Alzheimer's disease pathology, this study aimed to determine whether artemisinin (ART) counteracts Aβ1-42-induced neurotoxicity through the targeted activation of AMPK signaling. This work provides critical mechanistic insights supporting the therapeutic repurposing of ART for AD intervention.</p><p><strong>Methods: </strong>Therefore, Aβ1-42-insulted PC12 catecholaminergic, SH-SY5Y neuroblastoma, and primary neuronal cell cultures were used to assess the neuroprotective effects of ART. Compound C and shAMPK were used to confirm AMPK dependency. In vivo efficacy was assessed with 3xTg-AD mice.</p><p><strong>Results: </strong>ART restored viability, reduced reactive oxygen species, stabilized mitochondrial function, and prevented apoptosis. AMPK was activated by ART in a dose- and time-dependent manner and was reversed by Compound C and shAMPK. In 3xTg-AD mice, ART elevated brain P-AMPK expression. Together, these results show that ART activates AMPK in relation to neuroprotection against Aβ-induced toxicity.</p><p><strong>Discussion: </strong>These findings collectively demonstrate that ART confers robust neuroprotection primarily via AMPK activation, thereby restoring redox homeostasis, preserving mitochondrial structural integrity, and suppressing caspase-dependent apoptosis. The high consistency of these therapeutic effects across complementary in vitro and in vivo models highlights the indispensable role of the AMPK cascade.</p><p><strong>Conclusion: </strong>Given its established clinical safety profile and high blood-brain barrier permeability, ART represents a compelling candidate for repurposing as a disease-modifying drug in AD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944327","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":"From Structural Resolution to Functional Elucidation: Research Progress of GPR158 as a Target for Antidepressant Drug Development.","authors":"Wei Guan, Ya-Bin Zheng","doi":"10.2174/011570159X478149260820102256","DOIUrl":"https://doi.org/10.2174/011570159X478149260820102256","url":null,"abstract":"<p><p>G Protein-Coupled Receptors (GPCRs) are the most widely used drug targets in neuropsychiatric disorders. GPR158, an orphan class C GPCR, is highly enriched in the central nervous system and has emerged as a critical regulator of stress-related depression. However, its precise mechanisms in depression remain incompletely understood. This review aims to establish a systematic framework spanning the molecular structure to physiological function, highlighting the role of GPR158 in the onset and progression of depression. We summarize the expression pattern, unique structural features, novel ligands, and downstream signaling pathways of GPR158, with a focused discussion on its multiple regulatory mechanisms in depression, including Cyclic Adeno-sine Monophosphate (cAMP) signaling, neuronal excitability, Brain-derived Neurotrophic Factor (BDNF) translation, glutamatergic transmission, and mitophagy. Abnormally upregulated GPR158 in the prefrontal cortex and hippocampus promotes depressive-like behaviours, whereas knockout or inhibition of GPR158 exerts antidepressant-like effects. These findings not only reveal the potential regulatory function of GPR158 in the pathological process of depression but also provide a solid theoretical basis for the development of antidepressant drugs targeting GPCRs, facilitating the subsequent development of more accurate and efficient antidepressant candidate drugs.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905287","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":"Gut Microbiota-Derived Metabolites in Cardiovascular and Neuropsychiatric Comorbidity: From Mechanistic Insights to Therapeutic Frontiers.","authors":"Yushen Guan, Jiahao Duan, Chun Yang, Xinying Zhang, Ling Yang","doi":"10.2174/011570159X478567260811105329","DOIUrl":"https://doi.org/10.2174/011570159X478567260811105329","url":null,"abstract":"<p><p>The growing comorbidity between cardiovascular and neuropsychiatric disorders presents a major global health challenge. This reciprocal interaction worsens patient prognosis and hinders the diagnosis and treatment of these comorbid conditions. In recent years, the concept of the \"gut-heart-brain axis\" has highlighted the central pathogenic and therapeutic role of the gut microbiota in linking these distal systems. This review therefore aims to clarify this axis and to explore how specific gut microbiota metabolites modulate this bidirectional physiological interaction. We have integrated recent research to elucidate how gut microbiota dysbiosis regulates cardiovascular-neuropsychiatric comorbidities through the following convergent pathways: gut barrier disruption leading to metabolic endotoxemia; NLRP3 inflammasome activation; adaptive immunity shifting towards Th17 cell dominance and suppressing regulatory T cells; hypothalamic-pituitary-adrenal axis overactivation; and autonomic nervous system dysfunction. We critically reviewed microbiome-targeted interventions, noting that although the existing literature provides reliable epidemiological associations and proof of concept in animal models, definitive causal relationships in human populations remain insufficiently confirmed. Establishing such causal relationships between specific microbial metabolites and the outcomes of chronic cardiovascular or neuropsychiatric diseases will require rigorous longitudinal and interventional studies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905246","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":"A Critical Review of the Interactions Between Δ9-THC and Other Naturally Occurring Phytochemical Constituents of Cannabis sativa.","authors":"Harrison J Elder, Bryan W Jenkins, C Austin Zamarripa, Tory R Spindle, Ryan Vandrey","doi":"10.2174/011570159X453562260805073318","DOIUrl":"https://doi.org/10.2174/011570159X453562260805073318","url":null,"abstract":"<p><strong>Introduction: </strong>This narrative review systematically examines the available empirical evidence for interactions between delta-9-tetrahydrocannabinol (Δ9-THC or THC) and C. sativa's other phytochemical constituents hypothesized to underpin the popular yet controversial notion of 'entourage effects' experienced with botanical cannabis. Many relevant preclinical and clinical studies have been conducted in the last decade to elucidate the individual contributions of various phytocannabinoids and bioactive terpenes to the pharmacodynamic effects of C. sativa. However, their varied methods and results complicate their interpretation. Here, a particular emphasis is placed on synthesizing data from clinical studies of THC's modulation by Cannabis sativa's other phytochemical constituents.</p><p><strong>Methods: </strong>A systematic search of the scientific literature indexed in PubMed was conducted to identify controlled clinical and preclinical studies evaluating the modulation of THC's effects by individual phytochemicals. Studies that evaluated the phytocannabinoids cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabichromene (CBC), and cannabis terpenes α-pinene, d-limonene, β-myrcene, linalool, α-humulene, β-caryophyllene, bisabolol, terpinene, and terpineol were included in the literature search for discussion.</p><p><strong>Results: </strong>Cannabidiol and THC interactions have been extensively studied, with recent findings showing significant exacerbation of THC effects when orally coadministered, but not when inhaled. Clinical studies examining THC interactions with constituents beyond CBD remain comparatively limited. Recent clinical evidence suggests that THCV may reduce certain subjective and cognitive effects of THC. At the same time, some terpenes, such as limonene, can selectively modulate adverse effects associated with high THC doses in humans. Clinical studies have often failed to translate the interactive effects between THC and minor phytocannabinoids/terpenes observed in animal models.</p><p><strong>Discussion: </strong>Although interest in the clinical pharmacology of minor cannabinoids and terpenes has grown in recent years, the evidence supporting meaningful modulation of THC's effects in humans remains exceptionally limited. The mixed results from preliminary studies underscore the complexity of phytochemical interactions and the inherent challenges of translating preclinical findings into measurable clinical outcomes.</p><p><strong>Conclusion: </strong>Well-designed, controlled clinical studies of individual phytochemical interactions on subjective, therapeutic, and adverse effects are still required to support entourage effects in humans. In particular, the effects of many bioactive terpenes and trace cannabinoids have not yet begun to be evaluated in humans, either as individual phytochemicals or when combined with THC.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905215","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":"Terazosin Alleviates Apoptosis and Neuroinflammation in Cerebral Ischemia-reperfusion Injury via Activating the PI3K/AKT/mTOR Signaling Pathway.","authors":"Linlin Xie, Yukun Ping, Jie Zhao, Qiong Wu, Yuwei Huang, Mingming Shang, Ludong Hu, Xiaobo Li","doi":"10.2174/011570159X477062260820053528","DOIUrl":"https://doi.org/10.2174/011570159X477062260820053528","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke remains a major cause of disability and death worldwide, and effective neuroprotective treatments are urgently needed. This study investigated whether Terazosin (TZ), a clinically approved drug with neuroprotective potential, ameliorated Cerebral Ischemia-Reperfusion Injury (CIRI) and explored the underlying mechanisms.</p><p><strong>Methods: </strong>This study integrated network pharmacology analysis with in vivo experimental validation to investigate the neuroprotective effects of TZ against CIRI. Neurological deficits, infarct volume, and brain edema were evaluated in mice. TTC, TUNEL, and Nissl staining, as well as Western blotting, immunofluorescence staining, and quantitative real-time PCR (qPCR), were used to evaluate cell apoptosis, inflammation, and the activity of the PI3K/AKT/mTOR signaling pathway. Potential targets associated with TZ and CIRI were obtained from public databases, followed by GO and KEGG enrichment analyses of the overlapping targets. Statistical analyses were performed using GraphPad Prism 10.1, and P < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>TZ treatment significantly reduced cerebral infarct volume and improved neurological function in a mouse MCAO/R model. It attenuated neuronal apoptosis, as evidenced by increased Bcl-2 expression and decreased Bax expression, and suppressed neuroinflammation, as indicated by reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and decreased microglial activation. Bioinformatics analysis identified 140 overlapping targets between TZ and CIRI, with PIK3CA, MTOR, and several other genes emerging as key hub genes. KEGG enrichment analysis revealed significant enrichment of the PI3K/AKT signaling pathway. Further mechanistic investigations revealed that TZ activated the PI3K/AKT/mTOR signaling pathway. Importantly, the neuroprotective effects of TZ were abolished by the PI3K inhibitor LY294002, supporting an essential role of this pathway in mediating the protective effects of TZ against CIRI.</p><p><strong>Discussion: </strong>These findings indicate that TZ may protect against CIRI by suppressing apoptosis and neuroinflammation through activation of the PI3K/AKT/mTOR signaling pathway, thereby providing preclinical evidence for its potential repurposing as a treatment for ischemic stroke.</p><p><strong>Conclusion: </strong>In summary, this study demonstrates that TZ exerts neuroprotective effects against CIRI by activating the PI3K/AKT/mTOR signaling pathway. These results provide a preclinical basis for repurposing TZ as a treatment for ischemic stroke and highlight the PI3K/AKT/mTOR axis as a potential neuroprotective target.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905225","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":"Statin Therapy for Primary Prevention in Adults Aged 80 Years and Older: A Systematic Review Conducted in Accordance with PRISMA 2020.","authors":"Francisco Epelde","doi":"10.2174/011570159X473652260816151554","DOIUrl":"https://doi.org/10.2174/011570159X473652260816151554","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Statins are well established for the primary prevention of cardiovascular disease (CVD) up to approximately 75 years of age; however, direct evidence in adults aged 80 years and older remains limited. Extrapolation from younger populations is uncertain because advanced age is associated with greater competing mortality, frailty, multimorbidity, polypharmacy, and a shorter remaining time in which benefit can accrue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a systematic review in accordance with PRISMA 2020. A prespecified protocol was developed before screening. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched through October 12, 2025. Eligible evidence comprised randomized trials, age-stratified trial analyses, pooled or individual-participant meta-analyses, systematic reviews with age-stratified quantitative data, and adjusted observational cohorts of older adults without established atherosclerotic cardiovascular disease. Outcomes included major adverse cardiovascular events (MACE), myocardial infarction, stroke, all-cause and cardiovascular mortality, adverse events, cognition, disability, and functional outcomes. Risk of bias or methodological quality was assessed using RoB 2, the Newcastle-Ottawa Scale, or AMSTAR 2, as appropriate, and certainty of evidence was rated using GRADE.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twelve studies or trial programs met the inclusion criteria. Randomized evidence directly applicable to adults aged 80 years and older was minimal. PROSPER enrolled participants up to 82 years of age but combined primary and secondary prevention; ALLHAT-LLT showed no benefit in adults aged 75 years and older; and JUPITER and HOPE-3 showed reductions in cardiovascular events among adults aged 70 years and older but included few octogenarians. Observational cohorts suggested lower mortality or cardiovascular event rates among statin users, although these estimates were limited by healthy-user bias, residual confounding, and heterogeneity in age strata and outcome definitions. A formal meta-analysis of the primary-prevention population aged 80 years and older was not feasible because no randomized trial provided a directly comparable, extractable estimate for this group and the observational estimates were clinically and methodologically heterogeneous.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Evidence supports statin benefit through approximately 75 years of age, but evidence beyond 80 years is indirect and of low to very low certainty. Benefit is most plausible in robust octogenarians at high cardiovascular risk who have sufficient life expectancy, whereas routine initiation is unlikely to offer meaningful benefit to frail adults with a limited prognosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Current evidence is insufficient to support routine statin initiation for primary prevention in all adults aged 80 years and older. Decisions should be individualized through shared decision-making that consid","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905293","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":"Association of Androgen Deprivation Therapy with Cerebral Small Vessel Disease Burden in Prostate Cancer.","authors":"Longhai Zeng, Rentang Bi, Zijun Yang, Qian Liu, Yanmei Qiu, Yanhao Wei, Haokun Peng, Wenbin Xiong, Bo Hu, Ya'nan Li","doi":"10.2174/011570159X477221260817120345","DOIUrl":"https://doi.org/10.2174/011570159X477221260817120345","url":null,"abstract":"<p><strong>Introduction: </strong>Androgen Deprivation Therapy (ADT) is essential for advanced Prostate Cancer (PCa) but may increase cardiovascular and cerebrovascular risks. Its adverse effects on cerebral small vessels remain unclear. Leukoaraiosis (LA) and Lacunar Infarction (LI) are neuroimaging markers of Cerebral Small Vessel Disease (CSVD) associated with cognitive decline and stroke.</p><p><strong>Methods: </strong>This retrospective analysis used data from the multi-center SMART cohort (13 hospitals, 2014-2025) to examine associations between ADT exposure and CSVD burden using multivariate logistic regression, with stratified analyses by treatment duration and modality. Mediation analysis assessed the statistical role of systemic inflammation.</p><p><strong>Results: </strong>PCa patients receiving ADT (n=210) had a significantly higher risk of LA (adjusted OR=1.59, 95% CI: 1.15-2.20) compared to non-ADT users (n=1,181), but no significant increase in LI risk was observed. In the statistical mediation analysis, the Systemic Inflammation Response Index (SIRI) accounted for 27.21% of the observed association between ADT and LA. A duration-dependent association was evident, with significantly elevated LA risks in patients receiving medium-long term (12-24 months) and long-term (>24 months) ADT.</p><p><strong>Discussion: </strong>These findings suggest that ADT is associated with increased cerebral small vessel injury, particularly LA. The duration-dependent association and the statistical association involving systemic inflammation are consistent with a potential pathway linking ADT to cerebrovascular damage, but causality cannot be inferred. Monitoring cerebrovascular health and inflammatory markers in patients on prolonged ADT may aid risk stratification.</p><p><strong>Conclusion: </strong>In this retrospective analysis of PCa patients without prior cardiovascular or cerebrovascular disease, ADT was associated with an increased burden of early LA in a duration-dependent manner, with systemic inflammation statistically accounting for part of this association.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079721","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}