Unraveling the complex interplay between glymphatic function, age, and brain structure in school-aged children with...

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition. The relationship between glymphatic dysfunction, brain structure, and age in ASD children is poorly understood, hindering targeted interventions. A total of 130 participants, including 67 children with ASD and 63 typically developing (TD) children, were enrolled in this research. Glymphatic function was assessed using diffusion tensor image analysis along the perivascular space (ALPS). Voxel-based morphometry was employed to measure gray matter volume (GMV). Statistical analyses were conducted to explore correlations between age, ALPS indices, and GMV, and to assess whether age moderates these relationships. Our results showed that children with ASD exhibited reduced glymphatic function, with significant differences in the ALPS_L index (P = 0.024) and ALPS_Bi index (P = 0.025) indices compared to TD children. The ALPS index was positively correlated with age (P < 0.05) and negatively correlated with GMV, particularly in regions linked to social and cognitive processing. The moderation analysis revealed that age moderated the relationship between the ALPS index and GMV, showing that the negative association between them weakened with increasing age. Receiver operating characteristic (ROC) curve analysis indicated that the ALPS index effectively distinguishes ASD from TD children (ALPS_L index area under the curve (AUC) = 0.710, ALPS_Bi index AUC = 0.712). Our study suggests that glymphatic dysfunction in children with ASD may be age-dependent, influencing brain structure, particularly GMV. The ALPS index holds potential as a diagnostic biomarker for early detection of ASD-related neurobiological changes, with implications for targeted therapeutic interventions.