{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:13:31Z","timestamp":1792800811004,"version":"4.5.0"},"reference-count":46,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Long-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Cancer treatment exposures were abstracted from medical records. Chronic health conditions were graded using Common Terminology Criteria for Adverse Events version 4.03.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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;\u20091316 participants), central nervous system (CNS) tumors (488 participants), and Hodgkin lymphoma (HL;\u2009571 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,\u20091.97; 95% CI, 1.33-2.90) and alkylator chemotherapy greater than or equal to 8000 mg\/m\n 2<\/jats:sup>\n in ALL survivors treated without CRT (RR,\u20092.80; 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.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.16077","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T11:33:30Z","timestamp":1685532810000},"page":"e2316077","source":"Crossref","is-referenced-by-count":71,"title":["Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors"],"prefix":"10.1001","volume":"6","author":[{"given":"Nicholas S.","family":"Phillips","sequence":"first","affiliation":[{"name":"Epidemiology and Cancer Control Department, St Jude Children\u2019s Research Hospital, Memphis, 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