{"doi":"10.1002/jmri.27774","title":"Exposure to Repetitive Head Impacts Is Associated With Corpus Callosum Microstructure and Plasma Total Tau in Former Professional American Football Players","abstract":"BACKGROUND: Exposure to repetitive head impacts (RHI) is associated with an increased risk of later-life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown. PURPOSE: To investigate whether RHI exposure is associated with later-life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning. STUDY TYPE: Retrospective cohort study. POPULATION: Seventy-five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms. FIELD STRENGTH/SEQUENCE: Diffusion-weighted echo-planar MRI at 3 T. ASSESSMENT: Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self-report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free-water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1-7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT-A) and Part B (TMT-B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF-A). STATISTICAL TESTS: Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures. RESULTS: RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P < 0.05) in TMT-A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT-B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P < 0.05) in TMT-A (FA, r = 0.36; AD, r = 0.28), TMT-B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29). DATA CONCLUSION: These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1.","journal":"Journal of Magnetic Resonance Imaging","year":2021,"id":181248,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273472,"name":"Lauren J. O’Donnell","orcid":"0000-0003-0197-7801","position":1,"is_corresponding":false},{"id":273468,"name":"Fan Zhang","orcid":"0000-0002-5032-6039","position":2,"is_corresponding":false},{"id":451321,"name":"Elena M. Bonke","orcid":"0000-0002-8547-7283","position":3,"is_corresponding":false},{"id":274932,"name":"Nico Sollmann","orcid":"0000-0002-8120-2223","position":4,"is_corresponding":false},{"id":271279,"name":"Yorghos Tripodis","orcid":"0000-0003-2190-7608","position":5,"is_corresponding":false},{"id":710524,"name":"Tim L. T. Wiegand","orcid":"0009-0009-6897-0939","position":6,"is_corresponding":false},{"id":274931,"name":"David Kaufmann","orcid":"0000-0002-9465-1263","position":7,"is_corresponding":false},{"id":732048,"name":"Lisa F. Umminger","orcid":null,"position":8,"is_corresponding":false},{"id":411186,"name":"Maria A. Di Biase","orcid":"0000-0002-7100-651X","position":9,"is_corresponding":false},{"id":718160,"name":"Elisabeth Kaufmann","orcid":"0000-0002-7582-2215","position":10,"is_corresponding":false},{"id":274927,"name":"Vivian Schultz","orcid":"0009-0006-0938-8154","position":11,"is_corresponding":false},{"id":68034,"name":"Michael L. Alosco","orcid":"0000-0002-8113-8428","position":12,"is_corresponding":false},{"id":306392,"name":"Brett Martin","orcid":null,"position":13,"is_corresponding":false},{"id":274934,"name":"Alexander Lin","orcid":"0000-0001-8236-880X","position":14,"is_corresponding":false},{"id":640015,"name":"Michael J. Coleman","orcid":"0000-0001-9326-7932","position":15,"is_corresponding":false},{"id":273470,"name":"Yogesh Rathi","orcid":"0000-0002-9946-2314","position":16,"is_corresponding":false},{"id":311510,"name":"Ofer Pasternak","orcid":"0000-0002-7078-6446","position":17,"is_corresponding":false},{"id":432469,"name":"Sylvain Bouix","orcid":"0000-0003-1326-6054","position":18,"is_corresponding":false},{"id":304496,"name":"Robert A. Stern","orcid":"0000-0002-5008-077X","position":19,"is_corresponding":false},{"id":274933,"name":"Martha E. Shenton","orcid":"0000-0003-4235-7879","position":20,"is_corresponding":false},{"id":274926,"name":"Inga K. Koerte","orcid":"0000-0003-1281-9286","position":21,"is_corresponding":false},{"id":276497,"name":"Janna Kochsiek","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-18T23:48:01.257885Z","pmid":"34137112","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":[]}