{"doi":"10.1001/jamanetworkopen.2023.16077","title":"Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors","abstract":"Importance: Long-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood. Objective: To determine whether aging adult childhood cancer survivors report more new-onset neurocognitive impairments compared with their siblings and to identify risk factors associated with such impairments. Design, Setting, and Participants: Participants of this cohort study included adult survivors of childhood cancer from the Childhood Cancer Survivor Study and their siblings as a control group. The original cohort included survivors who received a diagnosis between January 1, 1970, and December 31, 1986, for whom longitudinal neurocognitive assessment was available. This study examined the prevalence of new-onset neurocognitive impairment between baseline (23.4 years after diagnosis) and follow-up (35.0 years after diagnosis). The analysis was performed from January 2021 to May 2022. Exposures: Cancer treatment exposures were abstracted from medical records. Chronic health conditions were graded using Common Terminology Criteria for Adverse Events version 4.03. Main Outcomes and Measures: The primary outcome was new-onset (present at follow-up, but not present at baseline) neurocognitive impairment (defined as a score in the worst 10% of the sibling cohort). Impairment was assessed using the Childhood Cancer Survivor Study Neurocognitive questionnaire. Relative risks (RRs) and 95% CIs were used to estimate associations of neurocognitive impairment with treatment and health behaviors and conditions using generalized linear models. Results: The cohort comprised 2375 survivors (mean [SD] age at evaluation, 31.8 [7.5] years; 1298 women [54.6%]) of childhood cancer, including acute lymphoblastic leukemia (ALL; 1316 participants), central nervous system (CNS) tumors (488 participants), and Hodgkin lymphoma (HL; 571 participants). A total of 232 siblings (mean [SD] age at evaluation, 34.2 [8.4] years; 134 women [57.8%]) were included. Compared with siblings, a higher proportion of survivors with no impairment in memory at baseline had new-onset memory impairment at follow-up: siblings proportion, 7.8% (95% CI, 4.3%-11.4%); ALL survivors treated with chemotherapy only, 14.0% (95% CI, 10.7%-17.4%); ALL survivors treated with cranial radiation (CRT), 25.8% (95% CI, 22.6%-29.0%); CNS tumor survivors, 34.7% (95% CI, 30.0%-39.5%); and HL survivors, 16.6% (95% CI, 13.4%-19.8%). New-onset memory impairment was associated with CRT in CNS tumor survivors (RR, 1.97; 95% CI, 1.33-2.90) and alkylator chemotherapy greater than or equal to 8000 mg/m2 in ALL survivors treated without CRT (RR, 2.80; 95% CI, 1.28-6.12). Neurologic conditions mediated the impact of CRT on new-onset memory impairment in CNS survivors. Smoking, low educational attainment, and low physical activity were associated with elevated risk for new-onset memory impairment. Conclusions and Relevance: These findings suggest that adult survivors of childhood cancer are at elevated risk for late-onset memory impairment related to modifiable risk factors identified early in survivorship.","journal":"JAMA Network Open","year":2023,"id":319122,"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":58,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9212,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230925,"name":"Kayla Stratton","orcid":"0000-0002-5201-4565","position":1,"is_corresponding":false},{"id":570277,"name":"AnnaLynn M. Williams","orcid":"0000-0002-7042-5851","position":2,"is_corresponding":false},{"id":278735,"name":"Tim A. Ahles","orcid":"0000-0002-7936-2818","position":3,"is_corresponding":false},{"id":255612,"name":"Kirsten K. Ness","orcid":"0000-0002-2084-1507","position":4,"is_corresponding":false},{"id":362880,"name":"Harvey Jay Cohen","orcid":null,"position":5,"is_corresponding":false},{"id":478442,"name":"Kim Edelstein","orcid":"0000-0003-2648-4819","position":6,"is_corresponding":false},{"id":255628,"name":"Yutaka Yasui","orcid":"0000-0002-7717-8638","position":7,"is_corresponding":false},{"id":107382,"name":"Kevin C. Oeffinger","orcid":"0000-0003-0806-7894","position":8,"is_corresponding":false},{"id":371465,"name":"Eric J. Chow","orcid":"0000-0001-7712-961X","position":9,"is_corresponding":false},{"id":310246,"name":"Rebecca M. Howell","orcid":"0000-0002-0803-071X","position":10,"is_corresponding":false},{"id":230935,"name":"Leslie L. Robison","orcid":"0000-0001-7460-8578","position":11,"is_corresponding":false},{"id":230934,"name":"Gregory T. Armstrong","orcid":"0000-0001-8722-4207","position":12,"is_corresponding":false},{"id":230926,"name":"Wendy M. Leisenring","orcid":"0000-0001-7405-0906","position":13,"is_corresponding":false},{"id":230931,"name":"Kevin R. Krull","orcid":"0000-0002-0476-7001","position":14,"is_corresponding":false},{"id":720267,"name":"Nicholas S. Phillips","orcid":"0000-0002-2021-4036","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:07:12.004111Z","pmid":"37256617","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":[]}