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Background <p>Although combined antiretroviral therapy (cART) effectively suppresses viral replication, HIV-associated neurocognitive disorders (HAND) remain prevalent. The choroid plexus, as a viral reservoir, and the glymphatic system, as a brain fluid clearance pathway, may play key roles in HAND pathogenesis.However, no study has comprehensively assessed glymphatic system abnormalities and their clinical relevance in HAND. This study aimed to explore the relationship between early brain structural changes and glymphatic system dysfunction, as well as cognitive decline in HAND.</p> Methods <p>This study included 140 patients with intact cognition (IC), 129 patients with asymptomatic neurocognitive impairment (ANI), and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI), single- and multi-shell diffusion weighted imaging (DWI) data were used to assess choroid plexus and subcortical deep nuclei volumes, as well as glymphatic system function, including perivascular space volume fraction (PVSVF), free water in white matter (WM-FW), and diffusion tensor imaging along perivascular spaces (DTI-ALPS) index. We also analyzed the relationship between these indices and clinical features, and cognitive performance.</p> Results <p>Both IC and ANI groups showed significantly higher WM-FW compared to the HC group (<i>p</i> = 0.002 and <i>p</i> &lt; 0.001). The DTI-ALPS index differed significantly across the three groups (<i>p</i> &lt; 0.001), with reductions in both IC and ANI groups (both <i>p</i> &lt; 0.001), and further decline in the ANI group (<i>p</i> = 0.007). WM-FW was negatively correlated with information processing speed (<i>r</i> = -0.19, <i>p</i> = 0.032), while DTI-ALPS correlated positively with attention (<i>r</i> = 0.39, <i>p</i> &lt; 0.001) and language (<i>r</i> = 0.28, <i>p</i> = 0.001). There were no significant differences in choroid plexus or subcortical nuclei volumes.</p> Conclusion <p>This study provides a comprehensive evaluation of structural and glymphatic system function in HIV patients. WM-FW and DTI-ALPS may serve as non-invasive methods to screen for brain fluid circulation dysfunction. Multi-shell DWI shows higher sensitivity than single-shell sequences in detecting extracellular free water content.</p>

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Association of choroid plexus volume, glymphatic system markers, and cognitive impairment in HIV-associated neurocognitive disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Wenru Gong,
  • Zhongkai Zhou,
  • Ran Wang,
  • Ruichen Ren,
  • Chao Yuan,
  • Lingling Zhao,
  • Wei Wang,
  • Hongjun Li

摘要

Background

Although combined antiretroviral therapy (cART) effectively suppresses viral replication, HIV-associated neurocognitive disorders (HAND) remain prevalent. The choroid plexus, as a viral reservoir, and the glymphatic system, as a brain fluid clearance pathway, may play key roles in HAND pathogenesis.However, no study has comprehensively assessed glymphatic system abnormalities and their clinical relevance in HAND. This study aimed to explore the relationship between early brain structural changes and glymphatic system dysfunction, as well as cognitive decline in HAND.

Methods

This study included 140 patients with intact cognition (IC), 129 patients with asymptomatic neurocognitive impairment (ANI), and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI), single- and multi-shell diffusion weighted imaging (DWI) data were used to assess choroid plexus and subcortical deep nuclei volumes, as well as glymphatic system function, including perivascular space volume fraction (PVSVF), free water in white matter (WM-FW), and diffusion tensor imaging along perivascular spaces (DTI-ALPS) index. We also analyzed the relationship between these indices and clinical features, and cognitive performance.

Results

Both IC and ANI groups showed significantly higher WM-FW compared to the HC group (p = 0.002 and p < 0.001). The DTI-ALPS index differed significantly across the three groups (p < 0.001), with reductions in both IC and ANI groups (both p < 0.001), and further decline in the ANI group (p = 0.007). WM-FW was negatively correlated with information processing speed (r = -0.19, p = 0.032), while DTI-ALPS correlated positively with attention (r = 0.39, p < 0.001) and language (r = 0.28, p = 0.001). There were no significant differences in choroid plexus or subcortical nuclei volumes.

Conclusion

This study provides a comprehensive evaluation of structural and glymphatic system function in HIV patients. WM-FW and DTI-ALPS may serve as non-invasive methods to screen for brain fluid circulation dysfunction. Multi-shell DWI shows higher sensitivity than single-shell sequences in detecting extracellular free water content.