Dynamic brain glymphatic changes and cognitive function in COVID-19 recovered patients: a DTI-ALPS prospective cohort study

Abstract

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, 3, 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).

Conclusion: 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.

Keywords: COVID-19 recovered patients; DTI-ALPS; brain glymphatic function; cognitive function; fatigue.

Figure 1

Flowcharts for DSI image processing. (A) SWI image shows medullary vein; (B) Adjust the orientation of the lateral ventricle to better show the projection fibers and association fibers; (C) Brain extraction; (D) DTIfa image and the DTI color map shows the direction of projected fibers (z-axis, blue) and joint fibers (y-axis, green). Place two regions of interest (ROI) to measure the double ROI utilization of projection (projection) and associated (correlation) fibers.

Figure 2

Differences in DTI-ALPS Index Between COVID-19 Recovery Patients at Different Stages and Healthy Controls. DTI-ALPS: diffusion tensor image analysis along the perivascular space; HCs: healthy controls (Data for healthy controls (HCs) were collected at a single time point, with no longitudinal follow-up).

Figure 3

DTI-ALPS index—time curve and differences in DTI-ALPS index across different time periods. Compared to the follow-up 1 months and follow-up12 months, the follow-up 3 months showed an increase in the right brain DTI-ALPS index. Compared to the follow-up1 months, the follow-up 3 months exhibited a significant increase in the left brain DTI-ALPS index (Any common letters indicate no significant difference, while no common letters indicate a significant difference).

Figure 4

Correlation analysis results. (A,B) A positive correlation between bilateral DTI-ALPS index and MOCA scores in patients recovering for 3 months and HC patients. (C,D) A positive correlation between bilateral DTI-ALPS indices and mental exhaustion in patients recovering for 3 months and HC patients. DTI-ALPS, diffusion tensor image analysis along the perivascular space; MOCA, Montreal Cognitive Assessment.