Data Sheet 1_Neuroanatomical patterns of dementia risk in autism spectrum disorder.docx

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. While previous studies have reported a high prevalence of dementia diagnoses in the ASD population, the risk of dementia-related neurodegeneration remains poorly understood. This study aimed to assess dementia-sensitive composite measures of brain structure and brain age across the lifespan in an ASD cohort (ages 7–73) to investigate neuroanatomical features linked to neurodegenerative vulnerability. The composite score and brain age were not significantly different between diagnostic groups when analyses considered the entire cohort, nor when the cohort was split into subgroups based on age. However, age-effects were found for both groups, with negative relationships revealing a decrease in cortical thickness with increasing age. Subgroup analyses showed that the same negative relationship was evident in the old NT group but was absent in the old ASD group, even when controlling for clinical factors. Our findings are consistent with the safeguard or parallel development hypothesis and suggest that conventional dementia-like structural vulnerability is not widespread and generalizable in ASD. Our observations highlight the limitations of current dementia-sensitive composites in assessing neurodegenerative risk in ASD. Developing dementia-sensitive biomarkers for autistic individuals is critical to enhance diagnostic precision and identify clinically significant biomarkers in this cohort.