CNS Neuroscience & Therapeutics最新文献

{"title":"Neural Plasticity Induced by Working Memory Training: Insights From Cortical Microstructure and Transcriptional Profiles","authors":"Tian Zhang,&nbsp;Yuntao Gao,&nbsp;Yijun Li,&nbsp;Lin Wu,&nbsp;Xinxin Lin,&nbsp;Yilin Hou,&nbsp;Wei He,&nbsp;Yuanqiang Zhu,&nbsp;Jun Jiang,&nbsp;Yuanjun Xie,&nbsp;Peng Fang","doi":"10.1111/cns.70479","DOIUrl":"https://doi.org/10.1111/cns.70479","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the effects of an 8-week standardized computerized working memory training (WMT) program on cortical microstructure, morphometric similarity network (MSN) changes, and associated genetic factors in healthy adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 76 participants were divided into WMT and control groups. Cortical morphological measurements, including cortical thickness (CT) and fractional dimensions (FD), were measured. MSN changes based on CT and FD measures were analyzed. Additionally, partial least squares (PLS) analysis was conducted to investigate the relationship between critical microstructural alterations and gene transcript expression levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The WMT group exhibited reduced response times for updating, switching functions, and phonological loop tasks. The cortical morphological measurements revealed increases in CT in several right frontal regions, as well as FD in the frontopolar and middle frontal areas after WMT compared to baseline. Furthermore, significant decreases in MSN based on CT measures were found in specific occipital and intraparietal sulci. Similarly, the MSN of FD showed notable decreases in eigenvector and degree centrality in the left frontomarginal cortex and right middle temporal gyrus. PLS analysis revealed strong links between microstructural changes and gene expression, with PLS+ genes enriched in synaptic transmission, neural regulation, and energy metabolism, while PLS− genes were associated with intracellular transport, protein modification, and stress responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings highlight the subtle influences of WMT on brain structure and underlying biological processes, providing insights into its role in neural plasticity and suggesting potential genetic contributions to these structural changes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740259","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}

{"title":"Functional Disconnections of the Pre-Supplementary Motor Area in Patients With Post-Stroke Aphasia and Their Associations With Neurotransmitters","authors":"Daoran Wang,&nbsp;Xin Wang,&nbsp;Xinlei Xu,&nbsp;Kai Zheng,&nbsp;Dongdong Jiang,&nbsp;Guilan Huang,&nbsp;Lu Sun,&nbsp;Haobo Leng,&nbsp;Zimeng Yang,&nbsp;Guofu Zhang,&nbsp;Zhiyong Zhao,&nbsp;Caili Ren","doi":"10.1111/cns.70528","DOIUrl":"https://doi.org/10.1111/cns.70528","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pre-supplementary motor area (preSMA) is a critical region within domain-general networks involved in speech production. However, the impact of post-stroke aphasia (PSA) on functional reorganization in this area remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate alterations in functional connectivity (FC) of the preSMA in patients with PSA and their relationships with neurotransmitters and speech production recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted language assessments using the Western Aphasia Battery (WAB) on 31 patients with left hemisphere strokes at approximately 28 days and 3 months post-stroke. Functional magnetic resonance imaging (fMRI) was performed on all PSA patients and 22 normal controls (NCs) at baseline. We compared the FC of the bilateral preSMA between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to NCs, PSA patients exhibited decreased FC between the ipsilesional preSMA and the prefrontal-cingulate cortex, insula, and caudate, as well as between the contralesional preSMA and the prefrontal cortex and caudate. These FC changes were significantly associated with various neurotransmitters, particularly metabotropic glutamate, kappa opioid receptor, and cannabinoid receptor. Moreover, FC between the preSMA and the prefrontal-cingulate cortex showed negative correlation trends with changes in WAB-AQ and WAB subtests (naming, auditory comprehension, and repetition) at the three-month assessment. These findings were partially validated in an independent dataset (patients: <i>N</i> = 17; controls: <i>N</i> = 22).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest that functional connections of the preSMA are disrupted in PSA patients, which may be associated with neurotransmitter activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740167","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}

{"title":"APOE4 Exacerbates Cerebral Tau Pathology Through Cholesterol-Induced Degradation of Phosphatase in Atherosclerosis","authors":"Jiuyang Ding,&nbsp;Baofei Sun,&nbsp;Yang Gao,&nbsp;Cihang Gu,&nbsp;Jian Zhang,&nbsp;Li Wang,&nbsp;Jie Zheng,&nbsp;Bing Xia,&nbsp;Xiaolan Qi","doi":"10.1111/cns.70536","DOIUrl":"https://doi.org/10.1111/cns.70536","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Apolipoprotein epsilon4 allele (APOE4) is a common risk factor for atherosclerosis (AS) and neurodegenerative diseases like Alzheimer's disease (AD), but whether and how APOE4 induces AD-like neuropathies in the brain of AS pathology remains poorly characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By combining postmortem AS human brains and APOE4 knock-in mice, we examined the effects of APOE4 on tau and related neuropathological changes in the brain of AS. Behavioral and pathological observations were used to evaluate the protective effects of facilitating cholesterol transport in APOE4 AS mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we showed that APOE4 carriers exhibited higher AD-like phosphorylated Tau (p-Tau) levels in AS postmortem brains. Knocking in human APOE4 in high fat diet-fed mice induced AS pathology and coupled AS and AD. APOE4 promoted cerebral cholesterol content, which could trigger protein phosphatase 2A (PP2A) degradation. We further demonstrated cholesterol could facilitate the ubiquitination of PP2A B and PP2A C, which were regulatory and catalytic subunits of PP2A respectively, leading to PP2A B and PP2A C degradation through the ubiquitin-proteasome system. Reduced PP2A B and PP2A C resulted in cerebral Tau hyperphosphorylated at multiple AD-associated sites. The APOE4 AS mice exhibited an AD-like phenotype, including synaptic degeneration, blood-brain barrier breakdown, glial activation, and cognitive impairment simultaneously. Pharmacologically facilitating cholesterol transport alleviated neuropathologies in APOE4 AS mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Altogether, these results suggested a role of the APOE4 in linking AS with Tau neuropathology, which might increase the risk of related neurodegenerative diseases for AS patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740168","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}

{"title":"Mapping Divergent Subfield-Specific Hippocampal Degeneration in Mild Cognitive Impairment Continuum: Volumetric, Cognitive, and Genetic Predictors of Accelerated Hippocampal Biological Aging","authors":"Sadegh Ghaderi,&nbsp;Sana Mohammadi,&nbsp;Farzad Fatehi,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1111/cns.70548","DOIUrl":"https://doi.org/10.1111/cns.70548","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate hippocampal subfield atrophy and biological aging across the mild cognitive impairment (MCI) continuum, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 49 participants, categorized as cognitively normal (CN, <i>n</i> = 16), early MCI (EMCI, <i>n</i> = 16), or late MCI (LMCI, <i>n</i> = 17), underwent comprehensive neuroimaging, neuropsychological, and genetic assessments. High-resolution 3D T1-weighted MRI scans were processed using the volBrain platform and hippocampal subfield segmentation (HIPS) pipeline to quantify hippocampal subfield volumes and estimate biological age. Statistical analyses, including ANCOVA and stepwise regression, were employed to evaluate group differences and identify predictors of hippocampal biological age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results revealed significant volumetric reductions in LMCI, particularly within the CA1, CA4/dentate gyrus (DG), and stratum radiatum/lacunosum/moleculare (SRLM) subfields, with pronounced lateralized effects. Clinical and demographic covariates attenuated group differences in biological age, but volumetric adjustments highlighted a significant distinction between EMCI and LMCI, with EMCI exhibiting a higher biological age. Cognitive performance, as measured by the Montreal Cognitive Assessment (MoCA), emerged as a consistent predictor of biological age, while APOE ε4 carrier status was significantly elevated in LMCI patients. Regression analyses identified divergent contributions of CA2/3 (positively associated) and CA4/DG (negatively associated) volumes to biological age, underscoring the subfield-specific pathophysiological mechanisms. Asymmetry indices, although variably expressed across groups, offered limited predictive utility, with CA2/3 and CA4/DG asymmetries modestly influencing biological age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings support the integration of subfield-specific hippocampal volumetry and cognitive assessments in early diagnostic frameworks while highlighting the need for longitudinal studies to elucidate causal pathways linking subfield atrophy, biological aging, and cognitive decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716946","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}

{"title":"The Progression of NUS1-Associated Parkinson's Disease and the Diagnostic Potential of Plasma NgBR","authors":"Lizhi Li,&nbsp;Juanjuan Huang,&nbsp;Yaqin Xiang,&nbsp;Xuxiang Zhang,&nbsp;Qian Xu,&nbsp;Qiying Sun,&nbsp;Zhenhua Liu,&nbsp;Xinxiang Yan,&nbsp;Jinchen Li,&nbsp;Beisha Tang,&nbsp;Jifeng Guo","doi":"10.1111/cns.70549","DOIUrl":"https://doi.org/10.1111/cns.70549","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The study aimed to investigate the role of <i>NUS1</i> variants in Parkinson's disease (PD) progression and evaluate plasma Nogo-B receptor (NgBR) as a potential biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 228 PD patients, including 38 with <i>NUS1</i> variants (<i>NUS1</i>-PD) and 190 without (GU-PD), and all underwent at least two follow-up visits. Linear mixed-effects models assessed motor and non-motor symptom progression. Plasma NgBR levels were measured in PD, Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and healthy controls (HC), and receiver operating characteristic curve analysis evaluated its diagnostic efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>NUS1</i>-PD demonstrated an earlier age at onset and more severe motor features than GU-PD at baseline. Longitudinal analyses showed similar progression rates of UPDRS III and H&amp;Y stage (off-medication) in <i>NUS1</i>-PD and GU-PD, but a slower progression rate of urinary function in <i>NUS1</i>-PD (<i>p</i> = 0.024). Plasma NgBR levels were higher in PD than in HC, MSA, and PSP, with AUC values of 0.6832, 0.6716, and 0.6628, respectively. Plasma NgBR was associated with UPDRS III (<i>p</i> = 0.006) and cognitive impairment (<i>p</i> = 0.010).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>NUS1</i> variants show no impact on PD progression, while plasma NgBR may serve as a potential biomarker for PD diagnosis and clinical characteristics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716976","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}

{"title":"Cortical Hemodynamic Abnormalities Associated With Fine Motor Deficits in Mild Cognitive Impairment","authors":"Han Yang,&nbsp;Jing Teng,&nbsp;Yilun Qian,&nbsp;Taicheng Huang,&nbsp;Manyu Dong,&nbsp;Huanping Wang,&nbsp;Jie Song,&nbsp;Yuxuan Zhang,&nbsp;Mingming Zhang,&nbsp;Hanjun Liu,&nbsp;Ying Shen","doi":"10.1111/cns.70547","DOIUrl":"https://doi.org/10.1111/cns.70547","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Individuals with mild cognitive impairment (MCI) often exhibit progressive deficits in bimanual coordination and fine motor dexterity. However, the neural mechanisms underlying these motor impairments remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This cross-sectional study employed functional near-infrared spectroscopy (fNIRS) to examine cortical hemodynamic responses during fine motor tasks in MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty individuals with MCI and 40 age-, sex-, and education-matched healthy controls (HCs) performed the Nine-Hole Peg Test (NHPT) while fNIRS monitored oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) responses in the prefrontal cortex (PFC), sensorimotor cortex (SMC), and visual cortex (VC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to HCs, individuals with MCI exhibited significantly impaired NHPT performance, accompanied by reduced HbO responses in the right PFC and SMC during task performance. Furthermore, stepwise discriminant analysis identified a combination of right SMC HbO levels and NHPT scores as a significant predictor for distinguishing MCI from HCs, achieving an area under the curve (AUC) of 80.8%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide novel evidence linking aberrant cortical hypoactivation in the motor and executive control regions to fine motor impairments in individuals with MCI, suggesting disrupted motor-cognitive integration in early cognitive decline. The integration of fNIRS-derived hemodynamic responses with functional motor assessments offers a promising non-invasive approach for MCI detection and personalized rehabilitation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This study was registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2400082429) on March 28, 2024</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716704","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}

{"title":"Plasma Metabolites Link Non-Communicable Diseases to Increased White Matter Hyperintensities","authors":"Nan Wang,&nbsp;Baoshan Qiu,&nbsp;Weiqi Chen,&nbsp;Yuesong Pan,&nbsp;Yilong Wang","doi":"10.1111/cns.70507","DOIUrl":"https://doi.org/10.1111/cns.70507","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cerebral small vessel disease (CSVD) and non-communicable diseases (NCDs) are major global health burdens. White matter hyperintensities (WMH) are a key imaging feature of CSVD, but the relationship between WMH and NCDs, especially the role of plasma metabolites in this association, remains unclear. This study aims to elucidate this link.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included participants with WMH from the UK Biobank cohort and examined the prevalence of 29 common NCDs in this population. General linear regression was used to analyze the association between NCDs and WMH. Propensity score matching and elastic net regression identified plasma metabolites associated with NCDs. Mediation analysis was conducted to explore the role of these metabolites in the association between NCDs and WMH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 44,630 participants were included, of whom 47.0% were male. Approximately one-third of the participants had NCDs, with the most common being hypertension, dyslipidemia, and asthma. Compared to those without NCDs, the WMH volume in individuals with one or more comorbid NCDs was significantly increased by 18.43% to 68.15%. During a median follow-up of 9.5 years, individuals with hypertension, obstructive sleep apnea, and hypertension combined with coronary ischemic heart disease had significantly larger WMH volumes compared to those without NCDs, with increases of 30.81%, 36.44%, and 36.75%, respectively. Further analysis revealed that plasma metabolites associated with NCDs mediated this risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study elucidated the association between WMH and NCDs, showing that common NCDs significantly increase WMH volume. Plasma metabolites associated with NCDs mediate this risk. This provides new insights into preventing WMH progression in individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714800","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}

{"title":"Disrupted Glucose Metabolism Covariance Network in Amyotrophic Lateral Sclerosis","authors":"Xin Jin,&nbsp;Xueying Wang,&nbsp;Dingxin Zheng,&nbsp;Pubing Yuan,&nbsp;Jianyu Li,&nbsp;Ting Qiu,&nbsp;Huixiong Zhang,&nbsp;Yifan Chen,&nbsp;Jinfan Zhang,&nbsp;Feifei Wu,&nbsp;Qing Liu,&nbsp;Alessandro Grecucci,&nbsp;Yuanchao Zhang,&nbsp;Junling Wang,&nbsp;Xiaoping Yi,&nbsp;Lena Palaniyappan,&nbsp;B. Blair Braden","doi":"10.1111/cns.70537","DOIUrl":"https://doi.org/10.1111/cns.70537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to characterize the topological changes in glucose metabolism covariance networks in amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed the interregional coordination of ¹⁸F-FDG-PET data to examine topological alterations in individualized glucose metabolism covariance networks in 127 ALS patients compared to 128 healthy controls (HC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to HC, ALS patients showed reduced small-worldness (lower normalized clustering coefficient, higher normalized characteristic path length) and decreased global and local efficiency, suggesting impaired global integration and local segregation. These network metrics correlated with disease progression and motor function. Regionally, altered degree centrality affected motor and default mode networks, and related to GABAa and mGluR5 receptor expression. Transcriptomic associations further linked these changes to immune function, synaptic signaling, and protein regulation. Bidirectional shifts in connectivity strength were observed, with both increased connectivity and disease progression independently predicting reduced survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings may provide valuable biomarkers for monitoring the progression of ALS and suggest potential mechanistic pathways for the development of innovative therapeutic strategies for this disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716977","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}

{"title":"Assessment of the Impact of Statin Use to Predict All-Cause Mortality in Patients With Critical Cerebrovascular Disease: A Retrospective Cohort Study From the MIMIC-IV Database","authors":"Dong Tang,&nbsp;Zheng Huang,&nbsp;Shifu Li,&nbsp;Fenghua Chen","doi":"10.1111/cns.70542","DOIUrl":"https://doi.org/10.1111/cns.70542","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The impact of statin therapy on short-term mortality among critically ill patients with hemorrhagic stroke or ischemic stroke remains uncertain. We investigated associations between statin use and ICU and hospital mortality in this patient population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study using the MIMIC-IV database, including 6918 patients (2960 HS and 3958 IS) after applying strict exclusion criteria. Statin use was assessed by type, dose (standard vs. high), and initiation timing (pre-ICU vs. post-ICU). Survival outcomes were evaluated using Kaplan–Meier analysis and multivariable Cox regression models, landmark analyses, and Fine–Gray competing-risk models, with propensity score matching to adjust for confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Statin use significantly reduced ICU mortality at 30 days in HS (HR = 0.59, 95% CI: 0.41–0.87) and IS (HR = 0.45, 95% CI: 0.32–0.64) cohorts. Atorvastatin and simvastatin showed pronounced protective effects, independent of dose intensity. Post-ICU initiation of statins conferred greater benefit compared with pre-ICU initiation, especially in HS patients. Shorter statin treatment duration (≥ 3 days) sufficiently captured beneficial effects. Patients with hyperlipidemia demonstrated enhanced mortality benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Statin use is associated with significantly lower short-term mortality in critically ill stroke patients, supporting tailored strategies for optimal statin initiation and duration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714671","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}

{"title":"Effect of Probiotics Supplementation on REM Sleep Behavior Disorder and Motor Symptoms in Parkinson's Disease: A Pilot Study","authors":"Yitong Du,&nbsp;Lin Wang,&nbsp;Ying Cui,&nbsp;Xiaojiao Xu,&nbsp;Mingkai Zhang,&nbsp;Yue Li,&nbsp;Ting Gao,&nbsp;Dan Gao,&nbsp;Zhi Sheng,&nbsp;Shiya Wang,&nbsp;Houzhen Tuo","doi":"10.1111/cns.70541","DOIUrl":"https://doi.org/10.1111/cns.70541","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) patients experience gut microbiota dysbiosis. Probiotic intervention could potentially serve as a safe and effective adjunctive therapeutic approach for PD, but its effects on rapid eye movement sleep behavior disorder (RBD) and motor symptoms in PD patients warrant further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To examine the influence of probiotics on RBD, motor symptoms, gut microbiota, and serum metabolites in individuals with PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this randomized controlled trial, PD patients were randomly allocated to either a probiotics or a control group while maintaining standard treatments. Clinical outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) and RBD Questionnaire-Hong Kong (RBDQ-HK) were assessed at baseline and post-treatment. Furthermore, fecal and blood samples were collected from PD patients at both timepoints, with additional samples obtained from healthy controls for comparison. The 16S rRNA gene V3-V4 region sequencing method was used to analyze gut microbiota composition, and untargeted metabolomic techniques were utilized to assess serum metabolite alterations, followed by correlation analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty eligible PD patients were enrolled and randomly allocated into two groups. After 12 weeks of intervention, the probiotic group showed significant reductions in both UPDRS total scores (−4.8 ± 7.5 vs. 1.8 ± 13.1, <i>p</i> = 0.009) and RBDQ-HK scores (−7.5 ± 6.5 vs. 0 ± 5.8, <i>p</i> = 0.015) compared to controls. Gut microbiota analysis revealed increased abundance of <i>Actinobacteria</i>, <i>Negativicutes</i>, and <i>Bacillus</i>, with reductions in <i>Lactococcus</i>, <i>Comamonas</i>, and <i>Enterococcus</i> after probiotic intervention. Furthermore, compared to normal controls, PD patients exhibited 9 significantly elevated and 11 significantly reduced metabolites; probiotic intervention altered the serum metabolome in PD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrated probiotics' potential to ameliorate RBD and motor symptoms while positively affecting the composition of the gut microbiota and serum metabolites in PD patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714672","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}