Reduced Glymphatic Function in Autism Revealed by the Diffusion Tensor Analysis Along the Perivascular Space Index

Background The glymphatic system supports brain homeostasis by clearing interstitial solutes via perivascular pathways. Alterations in glymphatic function have been linked to neurodevelopmental and neurodegenerative disorders, but its role in autism spectrum disorder (ASD) remains unclear. Methods We analyzed diffusion tensor imaging (DTI) magnetic resonance imaging data from five cohorts in the Autism Brain Imaging Data Exchange (ABIDE) project. Glymphatic function was estimated using the DTI analysis along the perivascular space (ALPS) index. ASD diagnoses were confirmed according to DSM-IV-TR or DSM-5 criteria, and neurotypical (NT) participants had no history of neurological, psychiatric, or developmental disorders. Results The final sample comprised 250 participants (128 ASD, mean age = 18.57 ± 13.81; 122 NT, mean age = 21.32 ± 14.37). Two-way analysis of variance (ANOVA) revealed a significant main effect of diagnosis, F(1, 246) = 10.44, p = 0.0014, with lower ALPS-indices in ASD. A diagnosis-by-age interaction was also observed, F(1, 246) = 4.71, p = 0.031. Post hoc tests demonstrated that autistic adults (≥ 18 years) had significantly lower ALPS-indices than NT adults (p = 0.0004), whereas no group differences were demonstrated between younger ASD and NT (< 18 years). In ASD adults, the ALPS-index correlated negatively with depressive symptoms (r = − 0.489, p = 0.013), but not with IQ or autistic traits. Conclusions These findings suggest that glymphatic dysfunction in ASD may follow a developmental trajectory, with alterations becoming most evident in adulthood, potentially contributing to an increased risk of developing neurodegenerative disorder in autistic individuals.