{"doi":"10.1161/circulationaha.120.048202","title":"Neurocognitive Dysfunction and Smaller Brain Volumes in Adolescents and Adults With a Fontan Circulation","abstract":"Background: Neurocognitive outcomes beyond childhood in people with a Fontan circulation are not well defined. This study aimed to investigate neurocognitive functioning in adolescents and adults with a Fontan circulation and associations with structural brain injury, brain volumetry, and postnatal clinical factors. Methods: In a binational study, participants with a Fontan circulation without a preexisting major neurological disability were prospectively recruited from the Australia and New Zealand Fontan Registry. Neurocognitive function was assessed by using Cogstate software in 107 participants with a Fontan circulation and compared with control groups with transposition of the great arteries (n=50) and a normal circulation (n=41). Brain MRI with volumetric analysis was performed in the participants with a Fontan circulation and compared with healthy control data from the ABIDE I and II (Autism Brain Imaging Data Exchange) and PING (Pediatric Imaging, Neurocognition, and Genetics) data repositories. Clinical data were retrospectively collected. Results: Of the participants with a Fontan circulation who had a neurocognitive assessment, 55% were male and the mean age was 22.6 years (SD 7.8). Participants with a Fontan circulation performed worse in several areas of neurocognitive function compared with those with transposition of the great arteries and healthy controls ( P <0.05). Clinical factors associated with worse neurocognitive outcomes included more inpatient days during childhood, younger age at Fontan surgery, and longer time since Fontan procedure ( P <0.05). Adults with a Fontan circulation had more marked neurocognitive dysfunction than adolescents with a Fontan circulation in 2 domains (psychomotor function, P =0.01 and working memory, P =0.02). Structural brain injury was present in the entire Fontan cohort; the presence of white matter injury was associated with worse paired associate learning ( P <0.001), but neither the presence nor severity of infarct, subcortical gray matter injury, and microhemorrhage was associated with neurocognitive outcomes. Compared with healthy controls, people with a Fontan circulation had smaller global brain volumes ( P <0.001 in all regions) and smaller regional brain volumes in most cerebral cortical regions ( P <0.05). Smaller global brain volumes were associated with worse neurocognitive functioning in several domains ( P <0.05). A significant positive association was also identified between global brain volumes and resting oxygen saturations ( P ≤0.04). Conclusions: Neurocognitive impairment is common in adolescents and adults with a Fontan circulation and is associated with smaller gray and white matter brain volume. Understanding modifiable factors that contribute to brain injury to optimize neurocognitive function is paramount.","journal":"Circulation","year":2020,"id":61072,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9145,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322793,"name":"Joseph Yuan‐Mou Yang","orcid":"0000-0003-4081-7157","position":1,"is_corresponding":false},{"id":322794,"name":"Jian Chen","orcid":"0000-0002-0578-9675","position":2,"is_corresponding":false},{"id":324578,"name":"Adrian Schembri","orcid":null,"position":3,"is_corresponding":false},{"id":322795,"name":"Yves d’Udekem","orcid":"0000-0003-1851-7836","position":4,"is_corresponding":false},{"id":324579,"name":"Diana Zannino","orcid":null,"position":5,"is_corresponding":false},{"id":322796,"name":"Nadine A. Kasparian","orcid":"0000-0001-8075-6817","position":6,"is_corresponding":false},{"id":322797,"name":"Karin du Plessis","orcid":"0000-0003-0574-7878","position":7,"is_corresponding":false},{"id":322798,"name":"Stuart M. Grieve","orcid":"0000-0002-2712-157X","position":8,"is_corresponding":false},{"id":322799,"name":"Thomas Welton","orcid":"0000-0002-9503-2093","position":9,"is_corresponding":false},{"id":322800,"name":"Belinda Barton","orcid":"0000-0002-3157-2031","position":10,"is_corresponding":false},{"id":322801,"name":"Thomas L. Gentles","orcid":"0000-0001-6149-2596","position":11,"is_corresponding":false},{"id":322802,"name":"David S. Celermajer","orcid":"0000-0001-7640-0439","position":12,"is_corresponding":false},{"id":322803,"name":"Chantal Attard","orcid":"0000-0002-4428-1663","position":13,"is_corresponding":false},{"id":322804,"name":"Kathryn Rice","orcid":"0000-0002-1153-7052","position":14,"is_corresponding":false},{"id":322805,"name":"Julian Ayer","orcid":"0000-0003-4647-8061","position":15,"is_corresponding":false},{"id":322806,"name":"Simone Mandelstam","orcid":"0000-0001-6287-0819","position":16,"is_corresponding":false},{"id":44631,"name":"David Winlaw","orcid":"0000-0001-8005-3361","position":17,"is_corresponding":false},{"id":322807,"name":"Mark T. Mackay","orcid":"0000-0002-3787-1112","position":18,"is_corresponding":false},{"id":322808,"name":"Rachael Cordina","orcid":"0000-0001-7882-389X","position":19,"is_corresponding":false},{"id":322792,"name":"Charlotte E. Verrall","orcid":"0000-0003-4445-2124","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T21:09:27.985420Z","pmid":"33231097","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}