{"title":"黄斑绒毛膜毛细血管灌注区：小脑血管病患者轻度认知障碍的潜在生物标志物","authors":"Weitao Yu, Zeqi Shen, Weifen Zhang, Mengmeng Yue, Shouxuan Gao, Jiawei Ye, Wanmao Ni, Panpan Shen, Lujie Han, Shunyuan Guo, Jie Zheng, Liang Yu, Faliang Gao, Yu Geng, Chaoyang Hong, Sheng Zhang","doi":"10.1136/svn-2025-004139","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>To develop and validate retinal vascular biomarkers for detecting mild cognitive impairment (MCI) in cerebral small vessel disease (CSVD) using swept-source optical coherence tomography angiography (SS-OCTA).</p><p><strong>Methods: </strong>Participants with MCI and normal cognition were prospectively enrolled from two ongoing cohorts (Dream-10 and FRESH-CSVD; NCT06164262 and NCT06431711). All participants underwent SS-OCTA and structural MRI (S-MRI). Individuals with Alzheimer's disease were excluded based on plasma biomarkers. Participants were split into development (January-August 2024) and temporal validation (September 2024-January 2025) cohorts. Feature selection was conducted using least absolute shrinkage and selection operator regression, followed by receiver operating characteristic analyses.</p><p><strong>Results: </strong>A total of 209 participants were included, with 48.8% (102/209) diagnosed with MCI. In the development cohort (n=136), the 3-6 mm macular choriocapillaris perfusion area (CCPA) of the left eye (oculus sinister, OS) showed superior diagnostic accuracy for MCI (AUC=0.906), outperforming S-MRI markers (all p<i><</i>0.05). Temporal validation confirmed diagnostic accuracy (AUC 0.902; sensitivity 88.6%, specificity 81.3%) with minimal performance drift (ΔAUC 0.002). Adding S-MRI markers did not significantly enhance diagnostic performance (p>0.05). Both 0-3 and 3-6 mm OS macular CCPA were significantly associated with cognitive decline (Mini-Mental State Examination, Montreal Cognitive Assessment and Clinical Dementia Rating Sum of Boxes; all p<i><</i>0.01), and mediation analyses suggested partial effects through white matter hyperintensity volume and right choroid plexus volume ratio.</p><p><strong>Conclusion: </strong>SS-OCTA-derived macular CCPA, especially in the 3-6 mm OS region, may serve as a promising and non-invasive biomarker for CSVD-related MCI. Further multicentre studies are needed to establish its clinical applicability.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Macular choriocapillaris perfusion area: a potential biomarker of mild cognitive impairment in patients with cerebral small vessel disease.\",\"authors\":\"Weitao Yu, Zeqi Shen, Weifen Zhang, Mengmeng Yue, Shouxuan Gao, Jiawei Ye, Wanmao Ni, Panpan Shen, Lujie Han, Shunyuan Guo, Jie Zheng, Liang Yu, Faliang Gao, Yu Geng, Chaoyang Hong, Sheng Zhang\",\"doi\":\"10.1136/svn-2025-004139\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>To develop and validate retinal vascular biomarkers for detecting mild cognitive impairment (MCI) in cerebral small vessel disease (CSVD) using swept-source optical coherence tomography angiography (SS-OCTA).</p><p><strong>Methods: </strong>Participants with MCI and normal cognition were prospectively enrolled from two ongoing cohorts (Dream-10 and FRESH-CSVD; NCT06164262 and NCT06431711). All participants underwent SS-OCTA and structural MRI (S-MRI). Individuals with Alzheimer's disease were excluded based on plasma biomarkers. Participants were split into development (January-August 2024) and temporal validation (September 2024-January 2025) cohorts. Feature selection was conducted using least absolute shrinkage and selection operator regression, followed by receiver operating characteristic analyses.</p><p><strong>Results: </strong>A total of 209 participants were included, with 48.8% (102/209) diagnosed with MCI. In the development cohort (n=136), the 3-6 mm macular choriocapillaris perfusion area (CCPA) of the left eye (oculus sinister, OS) showed superior diagnostic accuracy for MCI (AUC=0.906), outperforming S-MRI markers (all p<i><</i>0.05). Temporal validation confirmed diagnostic accuracy (AUC 0.902; sensitivity 88.6%, specificity 81.3%) with minimal performance drift (ΔAUC 0.002). Adding S-MRI markers did not significantly enhance diagnostic performance (p>0.05). Both 0-3 and 3-6 mm OS macular CCPA were significantly associated with cognitive decline (Mini-Mental State Examination, Montreal Cognitive Assessment and Clinical Dementia Rating Sum of Boxes; all p<i><</i>0.01), and mediation analyses suggested partial effects through white matter hyperintensity volume and right choroid plexus volume ratio.</p><p><strong>Conclusion: </strong>SS-OCTA-derived macular CCPA, especially in the 3-6 mm OS region, may serve as a promising and non-invasive biomarker for CSVD-related MCI. Further multicentre studies are needed to establish its clinical applicability.</p>\",\"PeriodicalId\":48733,\"journal\":{\"name\":\"Journal of Investigative Medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Investigative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/svn-2025-004139\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Investigative Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/svn-2025-004139","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
目的：利用扫描源光学相干断层扫描血管成像技术（SS-OCTA）开发和验证视网膜血管生物标志物，用于检测脑小血管疾病（CSVD）患者的轻度认知障碍（MCI）。方法：前瞻性地从两个正在进行的队列（Dream-10和FRESH-CSVD； NCT06164262和NCT06431711）中招募MCI和认知正常的参与者。所有参与者均接受了SS-OCTA和结构MRI （S-MRI）检查。根据血浆生物标志物排除患有阿尔茨海默病的个体。参与者被分成发展组（2024年1月至8月）和时间验证组（2024年9月至2025年1月）。使用最小绝对收缩和选择算子回归进行特征选择，然后进行接收者操作特征分析。结果：共纳入209名受试者，其中48.8%（102/209）被诊断为轻度认知障碍。在发展队列（n=136）中，左眼（眼眼，OS） 3-6 mm黄斑绒毛膜毛细血管灌注区（CCPA）对MCI的诊断准确性更高（AUC=0.906），优于S-MRI标志物（均p0.05）。时间验证证实诊断准确（AUC 0.902，灵敏度88.6%，特异性81.3%），性能偏差最小（ΔAUC 0.002）。添加S-MRI标记物并没有显著提高诊断效能（p < 0.05）。0-3和3-6 mm OS黄斑CCPA均与认知能力下降显著相关（迷你精神状态检查、蒙特利尔认知评估和临床痴呆评分盒子总和，均p0.01），中介分析提示白质高强度体积和右侧脉络膜丛体积比有部分影响。结论：ss - octa来源的黄斑CCPA，特别是在3-6 mm OS区域，可能是一种有希望的非侵入性生物标志物，用于csvd相关MCI。需要进一步的多中心研究来确定其临床适用性。
Macular choriocapillaris perfusion area: a potential biomarker of mild cognitive impairment in patients with cerebral small vessel disease.
Aim: To develop and validate retinal vascular biomarkers for detecting mild cognitive impairment (MCI) in cerebral small vessel disease (CSVD) using swept-source optical coherence tomography angiography (SS-OCTA).
Methods: Participants with MCI and normal cognition were prospectively enrolled from two ongoing cohorts (Dream-10 and FRESH-CSVD; NCT06164262 and NCT06431711). All participants underwent SS-OCTA and structural MRI (S-MRI). Individuals with Alzheimer's disease were excluded based on plasma biomarkers. Participants were split into development (January-August 2024) and temporal validation (September 2024-January 2025) cohorts. Feature selection was conducted using least absolute shrinkage and selection operator regression, followed by receiver operating characteristic analyses.
Results: A total of 209 participants were included, with 48.8% (102/209) diagnosed with MCI. In the development cohort (n=136), the 3-6 mm macular choriocapillaris perfusion area (CCPA) of the left eye (oculus sinister, OS) showed superior diagnostic accuracy for MCI (AUC=0.906), outperforming S-MRI markers (all p<0.05). Temporal validation confirmed diagnostic accuracy (AUC 0.902; sensitivity 88.6%, specificity 81.3%) with minimal performance drift (ΔAUC 0.002). Adding S-MRI markers did not significantly enhance diagnostic performance (p>0.05). Both 0-3 and 3-6 mm OS macular CCPA were significantly associated with cognitive decline (Mini-Mental State Examination, Montreal Cognitive Assessment and Clinical Dementia Rating Sum of Boxes; all p<0.01), and mediation analyses suggested partial effects through white matter hyperintensity volume and right choroid plexus volume ratio.
Conclusion: SS-OCTA-derived macular CCPA, especially in the 3-6 mm OS region, may serve as a promising and non-invasive biomarker for CSVD-related MCI. Further multicentre studies are needed to establish its clinical applicability.
期刊介绍：
Journal of Investigative Medicine (JIM) is the official publication of the American Federation for Medical Research. The journal is peer-reviewed and publishes high-quality original articles and reviews in the areas of basic, clinical, and translational medical research.
JIM publishes on all topics and specialty areas that are critical to the conduct of the entire spectrum of biomedical research: from the translation of clinical observations at the bedside, to basic and animal research to clinical research and the implementation of innovative medical care.
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