Alterations in the Glymphatic System and Presence of Small Vessel Disease in Hospitalized and Non-Hospitalized COVID Patients: A Study of PSMD Index and DTI-ALPS

Abstract

Background: It is known that COVID-19 causes brain damage in the acute phase and leads to neurological complications such as dementia and brain fog in the chronic phase. Many factors have been implicated in these complications, including glymphatic system disorders, small vessel disease, and widespread inflammation. Peak width of skeletonized mean diffusivity (PSMD) is a sensitive biomarker for SVD, while the diffusion tensor image analysis along the perivascular space (DTI-ALPS) measures glymphatic system function. This study aims to investigate changes in PSMD and DTI-ALPS parameters in COVID-19 patients. Methods: Clinical and MRI data were obtained from the "neuroCOVID MRI dWI and fMRI with reversal learning" dataset, comprising 88 participants aged 19-65 years. Participants included 72 COVID-19-positive patients (30 hospitalized and 42 non-hospitalized) and 16 COVID-19-negative controls. None had neurological symptoms aside from anosmia. Neuropsychiatric symptoms were assessed using validated scales: depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9) and anxiety symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Cognitive functioning was evaluated using the Addenbrooke's Cognitive Examination (ACE-III), while executive functioning was measured with the Ineco Frontal Screening (IFS-Ch). Functional capacity was assessed using the Six Minute Walk Test (6MWT). MRI scans were processed to calculate PSMD and DTI-ALPS values. Statistical analyses compared hospitalized and non-hospitalized COVID-19 patients with controls using the Mann-Whitney U test and partial correlation analysis. Results: Hospitalized COVID-19 patients showed a significant increase in PSMD index values compared to controls indicating SVD. Non-hospitalized COVID-19 patients did not differ significantly from controls in PSMD values. No significant differences were found in DTI-ALPS values between any COVID-19 groups and controls. Additionally, there were no significant correlations between neurocognitive test scores and PSMD or DTI-ALPS values. Conclusion: Severe COVID-19 cases requiring hospitalization are associated with increased PSMD index values, suggesting the presence of small vessel disease even in the absence of overt neurological symptoms. Mild COVID-19 cases managed outpatiently do not exhibit significant SVD or glymphatic dysfunction.