{"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}
引用次数: 0
Abstract
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.