Glymphatic dysfunction in NAFLD patient: A preliminary magnetic resonance imaging study based on DTI-ALPS

Abstract

Objective: Whether there are alterations in the glymphatic system (GS) of patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aims to investigate alterations in GS function in patients with NAFLD and explore the relationship of these alterations with cognition and clinical indicators. Materials and Methods: Forty-three patients with pre-cirrhotic NAFLD (male: 37, mean age: 38.2 ± 6.7 years) and twenty-three age-, sex-, and education-matched controls (male: 17, mean age: 41.0 ± 6.7 years) underwent diffusion tensor imaging (DTI) examination and cognitive measurements. The DTI analysis along the perivascular space (DTI-ALPS) index, calculated from the DTI data, assessed differences in GS function between the two groups. Linear regression analysis examined the relationship between the ALPS index and Z-transformed cognitive scores. Spearman/Pearson correlation analysis was conducted for assessing the relationship of the ALPS index with clinical indicators. Results: After adjusted for age, sex, and BMI, NAFLD patients exhibited significantly lower ALPS index and higher diffusivity of projection fibers in the direction of the y-axis than controls (both P < 0.001). In the NAFLD group, the ALPS index was significantly correlated with the Mini-Mental State Examination score (beta [95% CI] = 2.123 [0.156, 4.091], P= 0.035) and the clock drawing score (beta [95% CI] = 4.233 [0.073, 8.393], P= 0.046) after adjusting for age, sex, body mass index, and education level. In addition, there was a significantly positive correlation between the ALPS index and visceral adipose tissue (r = 0.353, P= 0.020) after adjusting for age, sex, and BMI in NAFLD patients. Conclusion: Patients with NAFLD may exhibit glymphatic dysfunction prior to developing cirrhosis. Changes in the GS is associated with cognitive performance in NAFLD. These findings may contribute to understanding the mechanisms underlying cognitive impairment in NAFLD patients.