{
  "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.",
  "authors": [
    {
      "affiliations": [
        "The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China"
      ],
      "name": "Weitao Yu"
    },
    {
      "affiliations": [
        "Postgraduate Training Base Alliance, Wenzhou Medical University (Affiliated People’s Hospital), Hangzhou, Zhejiang, China"
      ],
      "name": "Zeqi Shen"
    },
    {
      "affiliations": [
        "The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China"
      ],
      "name": "Weifen Zhang"
    },
    {
      "affiliations": [
        "Postgraduate Training Base Alliance, Wenzhou Medical University (Affiliated People’s Hospital), Hangzhou, Zhejiang, China"
      ],
      "name": "Mengmeng Yue"
    },
    {
      "affiliations": [
        "Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Shouxuan Gao"
    },
    {
      "affiliations": [
        "School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Jiawei Ye"
    },
    {
      "affiliations": [
        "Cancer Center, Department of Pathology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Wanmao Ni"
    },
    {
      "affiliations": [
        "Department of the Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China"
      ],
      "name": "Panpan Shen"
    },
    {
      "affiliations": [
        "School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Lujie Han"
    },
    {
      "affiliations": [
        "Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Shunyuan Guo"
    },
    {
      "affiliations": [
        "Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Jie Zheng"
    },
    {
      "affiliations": [
        "Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Liang Yu"
    },
    {
      "affiliations": [
        "Center for Rehabilitation Medicine, Department of Neurosurgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Faliang Gao"
    },
    {
      "affiliations": [
        "Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Yu Geng"
    },
    {
      "affiliations": [
        "Center for Rehabilitation Medicine, Department of Ophthalmology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Chaoyang Hong"
    },
    {
      "affiliations": [
        "Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China"
      ],
      "name": "Sheng Zhang"
    }
  ],
  "title": "Macular choriocapillaris perfusion area: a potential biomarker of mild cognitive impairment in patients with cerebral small vessel disease",
  "uid": "347bc500-84d7-5287-826c-54c60217df0e"
}