Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

The glymphatic system is a recently discovered brain waste clearance system that is mostly active during sleep and disengaged during wakefulness. Impaired glymphatic function leads to the deposition of metabolic waste products in the brain potentially causing inflammation leading to various symptoms in ME/CFS. While the glymphatic function has been assessed in other neurodegenerative diseases using 'diffusion tensor imaging along the perivascular space' (DTI-ALPS), it has not been studied in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). This preliminary study investigates glymphatic function in 58 participants (ME/CFS = 31 and healthy controls = 27) using the DTI-ALPS index derived from DTI data acquired with 3 T MRI. The bilateral hemispheric DTI-ALPS index was estimated to assess glymphatic function, and an asymmetry index was calculated to determine interhemispheric asymmetry in glymphatic function. We found that the global DTI-ALPS index was significantly lower in ME/CFS patients compared to healthy controls (ME/CFS: 1.44 ± 0.086; healthy controls: 1.51 ± 0.11, p = 0.014), indicating reduced glymphatic function in ME/CFS. Examining the hemispheres separately, showed the right hemisphere DTI-ALPS index was lower in ME/CFS than healthy controls (ME/CFS = 1.41 ± 0.097; healthy controls = 1.49 ± 0.12; p = 0.009) but not different on the left. Additionally, we did not find any significant difference in asymmetry index between ME/CFS and healthy controls. We observed an association between the global DTI-ALPS index and severity of 'sleep disturbance' (p = 0.013, r = -0.47) and "impaired concentration" (p = 0.026, r = -0.43). This study demonstrated impaired glymphatic function in ME/CFS which may lead to symptoms such as cognitive dysfunction and sleep disturbance experienced by ME/CFS.