Glymphatic Function Alterations in Sleep Disorder Patients Post-COVID-19: A Longitudinal DTI-ALPS Study

Coronavirus disease-2019 (COVID-19) has led to widespread sleep disturbances, yet the link between post-COVID sleep problems and glymphatic-system function remains unclear.

Between January and March 2023, we enrolled 59 participants with newly developed sleep disorder after COVID-19 (COVID_SD; 24 males; median age 28 years) and 39 age-/sex-matched participants without such problems after COVID-19(COVID_NSD; 15 males; median age 25 y). Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI; 0-21, higher = poorer). All volunteers underwent brain magnetic-resonance imaging (MRI), including diffusion-tensor imaging (DTI), and computation of the DTI analysis along the perivascular space (DTI-ALPS) index. At two-month follow-up, 41 COVID_SD and 25 COVID_NSD participants were rescanned.

Baseline bilateral ALPS indices were lower in COVID_SD than in COVID_NSD (left 1.23 ± 0.08 vs 1.29 ± 0.11, p = 0.033; right 1.29 ± 0.08 vs 1.33 ± 0.11, p = 0.013). PSQI correlated negatively with ALPS (left r = -0.636, p = 0.0002; right r = -0.539, p < 0.0001). Over two months, ALPS increased and PSQI decreased, indicating partial recovery of glymphatic function alongside improved sleep.

Impaired glymphatic clearance is strongly associated with poorer sleep quality in participants with post-COVID sleep problems; improvement in sleep parallels restoration of DTI-ALPS indices.