Transl Psychiatry. 2025 Nov 17;15(1):475. doi: 10.1038/s41398-025-03655-2.
ABSTRACT
BACKGROUND: Individuals with autism spectrum disorder (ASD) and comorbid intellectual disability (ID) are particularly vulnerable to poor developmental trajectories. These individuals are at increased risk of Alzheimer’s disease (AD) relative to those without comorbid ID and the general population. Considering that there could be an important mechanistic link underlying ASD and AD, individuals with these conditions may stand to benefit from similar psychopharmacological treatments.
METHODS: This scoping review aimed to evaluate and synthesize the evidence on the effect of AD medications on neurocognitive outcomes in children and adolescents with ASD and low intelligence quotient (IQ). We performed the search according to PRISMA guidelines from inception to May 21st, 2025 in four databases: PubMed, PsycInfo, Scopus, and Web of Science. We included studies of children and adolescents (2 – 21 years) with ASD and low IQ (<85) treated with at least one Food and Drug Administration (FDA)-approved AD medication (donepezil, galantamine, rivastigmine, benzgalantamine, memantine, aducanumab, lecanemab or donanemab) and investigating neurocognitive outcomes.
RESULTS: Twelve studies met the eligibility criteria. Six studies reported on neurocognitive outcomes from N-methyl-D-aspartate (NMDA) receptor antagonist treatment and six studies from cholinesterase inhibitor treatment. Among studies reporting on cholinesterase inhibitors, significant improvement was detected in language (60% of five reporting studies), executive function (100% of two reporting studies), complex attention (100% of one reporting study), and general cognitive ability (50% of two reporting studies). Among the NMDA receptor antagonist studies, evidence of improvement was detected in language (60% of five reporting studies), executive function (75% of four reporting studies), learning and memory (100% of two reporting studies), perceptual-motor functioning (66.6% of three reporting studies), complex attention (100% of one reporting study), and general cognitive ability (50% of two reporting studies). Across studies, treatment with either a cholinesterase inhibitor or an NMDA receptor antagonist was associated with improvements in language, executive function, complex attention, and general cognitive ability. A pattern of significance was detected with age, in that younger children may benefit more from these medications than adolescents.
CONCLUSION: This scoping review identified promising evidence of neurocognitive improvement in children and adolescents with ASD and low IQ following treatment with either a cholinesterase inhibitor or an NMDA receptor antagonist. Considering the lack of FDA-approved treatments for the cognitive deficits associated with ASD and an absence of medications approved to treat core features of ASD, our findings highlight an opportunity for innovative directions in autism research and treatment.
PMID:41249122 | DOI:10.1038/s41398-025-03655-2
