Dynamic Brain Glymphatic Changes and Cognitive Function in COVID-19 Recovered Patients: A DTI-ALPS Prospective Cohort Study

Chengcheng He ¹ Jinmei Xie ¹ Weiwei Fang ² Yangyang Shi ¹ Baoqin Guo ¹ Anan Li ¹ Hao Liu ¹ Zhimin Zhu ¹ Wenrui Bao ³ Xuan Niu ³ Shaoyu Wang ⁴ Juan Fu ¹ Hua Li ^1,5* Wenjuan Xie ¹

• ¹ Department of Medical Imaging, Yulin Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Yulin, China
• ² 4th Hospital of Yulin, Yulin, Shaanxi Province, China
• ³ School of Future Technology, Xi'an Jiaotong University, Xi'an, China
• ⁴ MR Research Collaboration, Siemens Healthineers, Shanghai, China
• ⁵ The First People’s Hospital of Yulin, Yulin, Shaanxi Province, China

Objective: This study aimed to evaluate brain glymphatic function in COVID-19 recovered patients using the non-invasive Diffusion Tensor Imaging-Analysis Along the Perivascular Space (DTI-ALPS) technique. The DTI-ALPS technique was employed to investigate changes in brain glymphatic function in these patients and explore correlations with cognitive function and fatigue.Materials and Methods: Follow-up assessments were conducted at 1 month, 3 months, and 12 months post-recovery. A total of 31 patients completed follow-ups at all three time points, with 30 healthy controls (HCs) for comparison.Results: Compared to HCs, COVID-19 recovered patients showed a significant decline in MoCA scores at 3 months post-recovery (p< 0.05), which returned to near-normal levels by 12 months. mental fatigue, measured by the Fatigue Assessment Scale (FAS), was significantly higher in COVID-19 patients at all follow-up points compared to HCs (p < 0.05). The DTI-ALPS index in both hemispheres showed significant differences at 3 months post-recovery compared to HCs (p<0.001), indicating increased glymphatic activity. Longitudinal analysis revealed a peak in the DTI-ALPS index at 3 months post-recovery, which then decreased by 12 months. Correlation analysis showed a significant negative correlation between the Bilateral brain hemisphere DTI-ALPS index and MoCA scores (right side:r= -0.373, p=0.003; left side: r=-0.255, p=0.047), and a positive correlation with mental fatigue (right side:r=0.275, p=0.032; left side:r=0.317, p=0.013).This study demonstrates dynamic changes in brain glymphatic function in COVID-19 recovered patients, with a peak in activity at 3 months post-recovery. These changes are associated with cognitive function and mental fatigue, suggesting potential targets for addressing neurological symptoms of long COVID. The non-invasive DTI-ALPS technique proves to be a valuable tool for assessing brain glymphatic function in this population.