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Background <p>Lacunar infarction (LI), a subtype of ischemic stroke caused by cerebral small vessel disease (SVD), is strongly associated with post-stroke cognitive impairment (PSCI). While neuroimaging biomarkers are critical for diagnosis, their accessibility and cost limit routine use. The retina, as an extension of the central nervous system, offers a non-invasive window to study microvascular pathology. This study investigates the synergistic impact of infarct lesion volume and retinal microvascular metrics on cognitive impairment in LI patients.</p> Methods <p>We prospectively enrolled 112 LI patients and 128 controls. Retinal vascular parameters (tortuosity, vessel density, fractal dimension) were quantified from color fundus photographs, and lesion diameter was measured via MRI. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Linear regression models with generalized estimating equations (GEE) evaluated associations between retinal metrics, lesion diameter, and MoCA scores, adjusting for covariates (age, vascular risk factors). Interaction terms tested the moderating effects.</p> Results <p>LI patients exhibited sparser, more tortuous retinal microvasculature compared to controls (<i>p</i> &lt; 0.001). Poorer cognitive performance in LI was associated with larger lesion diameter (<i>p</i> &lt; 0.001) and retinal microvascular impairment. A significant interaction was observed between retinal microvasculature and lesion diameter on MoCA scores (fractal dimension: ß = 1.532, p for interaction = 0.026; vessel density: ß = 0.53, p for interaction = 0.041), suggesting that the relationship between lesion diameter and MoCA scores may be more pronounced in LI with severe retinal microvascular impairment.</p> Conclusions <p>The diameter of the lesion infarct and severity of retinal microvascular damage may jointly reflect global cognitive performance in LI, signifying ischemia as a potential shared mechanism. Integrating retinal imaging with neuroimaging may enhance early risk stratification and personalized intervention strategies.</p>

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Interactive effect of retinal microvascular impairment and larger lesion diameter on cognitive impairment in lacunar infarction

  • 期刊论文

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  • 发表日期：

    2026年1月26日

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  • William Robert Kwapong,
  • Jiahui Chen,
  • Zheli Chen,
  • Chunwen Zheng,
  • Yimo Guo,
  • Yuntao Liu,
  • Haoran Cheng,
  • Huihua Qiu,
  • Xiaoqian Luan,
  • Ip Yiu Ming Bonaventure,
  • Carol Y. Cheung,
  • Zhen Wang

摘要

Background

Lacunar infarction (LI), a subtype of ischemic stroke caused by cerebral small vessel disease (SVD), is strongly associated with post-stroke cognitive impairment (PSCI). While neuroimaging biomarkers are critical for diagnosis, their accessibility and cost limit routine use. The retina, as an extension of the central nervous system, offers a non-invasive window to study microvascular pathology. This study investigates the synergistic impact of infarct lesion volume and retinal microvascular metrics on cognitive impairment in LI patients.

Methods

We prospectively enrolled 112 LI patients and 128 controls. Retinal vascular parameters (tortuosity, vessel density, fractal dimension) were quantified from color fundus photographs, and lesion diameter was measured via MRI. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Linear regression models with generalized estimating equations (GEE) evaluated associations between retinal metrics, lesion diameter, and MoCA scores, adjusting for covariates (age, vascular risk factors). Interaction terms tested the moderating effects.

Results

LI patients exhibited sparser, more tortuous retinal microvasculature compared to controls (p < 0.001). Poorer cognitive performance in LI was associated with larger lesion diameter (p < 0.001) and retinal microvascular impairment. A significant interaction was observed between retinal microvasculature and lesion diameter on MoCA scores (fractal dimension: ß = 1.532, p for interaction = 0.026; vessel density: ß = 0.53, p for interaction = 0.041), suggesting that the relationship between lesion diameter and MoCA scores may be more pronounced in LI with severe retinal microvascular impairment.

Conclusions

The diameter of the lesion infarct and severity of retinal microvascular damage may jointly reflect global cognitive performance in LI, signifying ischemia as a potential shared mechanism. Integrating retinal imaging with neuroimaging may enhance early risk stratification and personalized intervention strategies.