The Physiology of Cognition in Autism Spectrum Disorder: Current and Future Challenges.

Cognitive impairment is among the most challenging characteristics of autism spectrum disorder (ASD). Although ASD is one of the common neurodevelopmental disorders, we are still behind in diagnosing and treating cognitive impairment in ASD. Cognitive impairment in ASD varies, meaning it could be at the sensory perception level to cognitive processing, learning, and memory. There are no diagnostic criteria for cognitive impairment that are specific to ASD. The leading causes of cognitive impairment in ASD could be neurological, immune, and gastrointestinal dysfunction. Immune dysfunction might lead to neuroinflammation, affecting neural connectivity, glutamate/gamma-aminobutyric acid (GABA) balance, and plasticity. The gut-brain axes are essential in the developing brain. Special retinal changes have recently been detected in ASD, which need clinical investigation to find their possible role in early diagnosis. Early intervention is crucial for ASD cognitive dysfunction. Due to the heterogeneity of the disease, the clinical manifestation of ASD makes it difficult for clinicians to develop gold-standard diagnostic and therapeutic criteria. We suggest a triad for diagnosis, which includes clinical tests for immune and gastrointestinal dysfunction biomarkers, clinical examination for the retina, and an objective neurocognitive evaluation for ASD, and to develop a treatment strategy involving these three aspects. Developing clear treatment criteria for cognitive impairment for ASD would improve the quality of life of ASD people and their caregivers and would delay or prevent dementia-related disorders in ASD people.