Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease

Rationale and Objectives To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. Materials and Methods A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. Results MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = −0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = −0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (−23.853 [−45.417, −2.289], P = 0.030) in MAFLD with MetS group. Conclusion MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS. To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = −0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = −0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (−23.853 [−45.417, −2.289], P = 0.030) in MAFLD with MetS group. MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.