Autism Spectrum Disorder and Perivascular Spaces: An Integrative Perspective Across the Lifespan

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent social communication difficulties, restricted interests, repetitive behaviors, and frequent medical comorbidities. Although early brain development in ASD has been extensively investigated, its biological progression across adulthood and aging remains largely unexplored. Growing evidence suggests that perivascular space (PVS) abnormalities may indicate impaired neurovascular integrity and reduced glymphatic clearance in ASD. Enlarged perivascular spaces (ePVS) in children commonly present alongside increased extra-axial CSF accumulation and more severe clinical manifestations, consistent with early alterations in CSF homeostasis and neuroimmune signaling. However, whether these abnormalities persist or evolve with aging remains unknown. Given that glymphatic and vascular integrity decline with age, and adults with ASD show elevated rates of sleep, metabolic, and cardiovascular disorders, PVS alterations may represent a unifying mechanism linking early neurodevelopmental divergence with later neurovascular vulnerability and cognitive aging. Advances in ultra-high-field MRI and automated segmentation now enable precise in vivo quantification of PVS burden, offering new opportunities for lifespan studies. By combining structural and functional methodologies, researchers may determine whether PVS constitute enduring traits, dynamic indicators of disease, or actionable therapeutic targets. Understanding their trajectories could provide critical insights into the continuum between neurodevelopmental and neurodegenerative phenomena in autism.